Signaling by PDGF (Homo sapiens)

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1, 17, 2011, 17, 29177, 17, 2317, 27201316, 203, 25251, 14, 171, 18, 22, 302, 172, 17, 26176, 17, 281, 8, 17171, 4, 17, 2417208, 171, 17, 1916, 205, 9, 17PI3K-catalyticsubunit [cytosol]Active PDGF dimers(AA, AB, BB)[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]PDGF A-chainprecursor dimer[Golgi membrane]Phospho-alphareceptor homodimer[plasma membrane]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Phospho- PDGFreceptor dimer[plasma membrane]PDGF A homodimer[extracellularregion]Active PDGF dimers(AA, AB, BB)[extracellularregion]Processed PDGF-B[extracellularregion]PDGF B homodimer[extracellularregion]Processed PDGF-B[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]PDGF A homodimer[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]p21 RAS:GDP [plasmamembrane]PDGF B homodimer[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]PDGF-D chainprecursor dimer[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Phospho- PDGFreceptor dimer[plasma membrane]STAT family members[cytosol]Active PDGF dimers(AA, AB, BB)[extracellularregion]cytosolPhospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]endoplasmic reticulum lumenNCK [cytosol]PDGF B homodimer[extracellularregion]PDGF-C chainprecursor dimer[Golgi membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]Phospho-betareceptor homodimer[plasma membrane]PDGF B homodimer[extracellularregion]Phospho- PDGFreceptor dimer[plasma membrane]PDGF B homodimer[extracellularregion]PDGF A/B heterodimer[extracellularregion]Processed PDGF-B[extracellularregion]PDGF:Phospho-PDGFreceptordimer:Crk:p130Cas:C3G[plasma membrane]PDGF A homodimer[extracellularregion]GRB2:SOS1 [cytosol]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]PDGF:phospho-PDGFreceptor dimer:STAT[plasma membrane]Collagen alpha-1(VI)chains[extracellularregion]PDGF A/B heterodimer[extracellularregion]Processed PDGF-B[extracellularregion]PDGF:Phospho-PDGFreceptor dimer[plasma membrane]Phospho- PDGFreceptor dimer[plasma membrane]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]PDGF AB or BBhomodimers[extracellularregion]PI3K-regulatorysubunit [cytosol]PDGF:Phospho-PDGFreceptor dimer:Crk[plasma membrane]PDGF A-chainprecursor dimer[Golgi membrane]Alpha-Beta receptorheterodimer [plasmamembrane]PDGF A/B heterodimer[extracellularregion]Heparan sulphate[extracellularregion]Processed PDGF-B[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]p21 RAS [plasmamembrane]Processed PDGF-B[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Processed PDGF-B[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]p21 RAS:GTP [plasmamembrane]Phospho PDGFalpha-betadimer:PDGF AB or BBdimers [plasmamembrane]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]PDGF A homodimer[extracellularregion]Phospho- PDGFreceptor dimer[plasma membrane]PDGF B homodimer[extracellularregion]Processed PDGF-B[extracellularregion]Alpha-Beta receptorheterodimer [plasmamembrane]PDGF B homodimer[extracellularregion]PDGF A homodimer[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]Collagenalpha-3(IV):Collagenalpha-4(IV):Collagenalpha-5(IV) triplehelix [extracellularregion]Active PDGF dimers(AA, AB, BB)[extracellularregion]PDGF AB precursorheterodimer[endoplasmicreticulum lumen]Processed PDGF-B[extracellularregion]PDGF A homodimer[extracellularregion]PDGF B homodimer[extracellularregion]PDGF B homodimer[extracellularregion]PDGF-D chainprecursor dimer[endoplasmicreticulum lumen]PDGF alpha/beta:PDGFAB and BB dimers[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]Processed PDGF-B[extracellularregion]PDGF A homodimer[extracellularregion]PDGF B homodimer[extracellularregion]Golgi lumenPDGF:Phospho-PDGFreceptor dimer:Src[plasma membrane]Phospho-alphareceptor homodimer[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]PDGF A/B heterodimer[extracellularregion]PDGF A homodimer[extracellularregion]PDGF A/B heterodimer[extracellularregion]PDGF precursordimers (AA, BB,A/B, CC, DD)[endoplasmicreticulum lumen]PDGF:Phospho-PDGFreceptordimer:Grb2:Sos1[plasma membrane]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]PDGF-D chainprecursor dimer[Golgi membrane]PDGF A homodimer[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]PDGF A/B heterodimer[extracellularregion]Active PDGF dimers(AA, AB, BB)[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]PDGF A and Bchains:ECM complex[extracellularregion]Beta receptorhomodimer [plasmamembrane]PDGF-D chain dimer[extracellularregion]PDGF:p-PDGFRdimer:p-PLCgamma[plasma membrane]PDGF A/B-chainprecursor heterodimer [Golgimembrane]PDGF B homodimer[extracellularregion]PDGF B homodimer[extracellularregion]PDGF:Phospho-PDGFreceptor dimer:Crk[plasma membrane]Phospho- PDGFreceptor dimer[plasma membrane]CRK, CRKL [cytosol]PDGF A and B chainswith retention motif[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Thrombospondin[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]PDGF A homodimer[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Active PDGF dimers(CC, DD)[extracellularregion]PDGF A homodimer[extracellularregion]PDGF-C chainprecursor dimer[Golgi membrane]PDGF B homodimer[extracellularregion]PDGF B-chainprecursor dimer[Golgi membrane]Phospho- PDGFreceptor dimer[plasma membrane]PI3K [cytosol]CRK, CRKL [cytosol]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]PDGF A homodimer[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Phospho- PDGFreceptor dimer[plasma membrane]PI3K-regulatorysubunit [cytosol]PDGF betareceptor:PDGF chainB homodimer [plasmamembrane]PI3K-catalyticsubunit [cytosol]PDGF receptor dimer[plasma membrane]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]PDGF:PDGF receptordimer [plasmamembrane]Processed PDGF-B[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]PDGF B homodimer[extracellularregion]Processed PDGF-B[extracellularregion]Processed PDGF-B[extracellularregion]Phospho-betareceptorhomodimer:GAP[plasma membrane]PDGF A isoforms[endoplasmicreticulum lumen]PDGF:Phospho-PDGFreceptor dimer[plasma membrane]PDGF:Phospho-PDGFreceptordimer:phospho-Src[plasma membrane]p21 RAS [plasmamembrane]Processed PDGF-B[extracellularregion]PDGF A homodimer[extracellularregion]PDGF A/B heterodimer[extracellularregion]PDGF:Phospho-PDGFRreceptor dimer:Nck[plasma membrane]Phospho PDGF alphareceptor:PDGF dimers[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Type IV collagen[extracellularregion]PDGF A/B heterodimer[extracellularregion]Phospho- PDGFreceptor dimer[plasma membrane]Extracellular matrixligands[extracellularregion]PDGF B homodimer[extracellularregion]Processed PDGF-B[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]PDGF A/B heterodimer[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]PDGF B-chainprecursor dimer[Golgi membrane]PDGF A/B heterodimer[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]Alpha receptorhomodimer [plasmamembrane]PDGF A homodimer[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Phospho-alphareceptor homodimer[plasma membrane]PDGF precursordimers (AA, BB, A/B,CC, DD) [Golgimembrane]Phospho-alphareceptor homodimer[plasma membrane]Collagenalpha-1(IV):Collagenalpha-2(IV)[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]PDGF A homodimer[extracellularregion]Phospho PDGF betareceptor: PDGF chainB homodimer [plasmamembrane]Phospho- PDGFreceptor dimer[plasma membrane]PDGF A/B heterodimer[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]Phospho-betareceptor homodimer[plasma membrane]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]Processed PDGF-B[extracellularregion]Phospho PDGF betareceptor: PDGF chainB homodimer [plasmamembrane]Tropocollagen typeVI [extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]Collagen type IX[extracellularregion]PDGF A-chainprecursor dimer[endoplasmicreticulum lumen]PDGF:Phospho-PDGFreceptor dimer[plasma membrane]Alpha receptorhomodimer [plasmamembrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]Processed PDGF-B[extracellularregion]PDGF-C chainprecursor dimer[extracellularregion]Processed PDGF-B[extracellularregion]PDGF B homodimer[extracellularregion]Beta receptorhomodimer [plasmamembrane]Novel PDGF precursordimers (CC, DD)[Golgi membrane]Classical PDGFprecursor dimers(AA, AB, BB) [Golgimembrane]Phospho-alphareceptor homodimer[plasma membrane]Phospho- PDGFreceptor dimer[plasma membrane]PDGF A homodimer[extracellularregion]Collagens[extracellularregion]Novel PDGF precursordimers (CC, DD)[extracellularregion]PDGF A/B-chainprecursor heterodimer [Golgimembrane]PDGF AB or BBhomodimers[extracellularregion]Phospho- PDGFreceptor dimer[plasma membrane]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]Processed PDGF-B[extracellularregion]PDGF A/B heterodimer[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]Processed PDGF-B[extracellularregion]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]PDGF A isoforms[Golgi membrane]PDGF:Phospho-PDGFreceptor dimer:Grb7[plasma membrane]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]PDGF A/B heterodimer[extracellularregion]PDGF A/B heterodimer[extracellularregion]Processed PDGF-B[extracellularregion]PDGF A/B heterodimer[extracellularregion]Phospho-betareceptor homodimer[plasma membrane]PDGF A/B heterodimer[extracellularregion]PDGF-C chainprecursor dimer[endoplasmicreticulum lumen]PDGF-D chainprecursor dimer[Golgi membrane]PDGF:Phospho-PDGFreceptor dimer[plasma membrane]PDGF B homodimer[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]Activeplatelet-derivedgrowth factor Achain isoforms[extracellularregion]PDGF:Phospho-PDGFreceptor dimer:PI3K[plasma membrane]PDGF A isoforms[Golgi membrane]PDGF:Phospho-PDGFreceptor dimer[plasma membrane]PDGF B homodimer[extracellularregion]PDGF A/B heterodimer[extracellularregion]Active PDGF dimers(AA, AB, BB)[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]Phospho-alphareceptor homodimer[plasma membrane]PDGF A homodimer[extracellularregion]Active PDGF dimers(AA, AB, BB)[extracellularregion]PDGF-C chain dimer[extracellularregion]PDGF B homodimer[extracellularregion]PDGF:Phospho-PDGFreceptor dimer[plasma membrane]Processed PDGF-B[extracellularregion]PDGF B homodimer[extracellularregion]PDGF:Phospho-PDGFreceptor dimer[plasma membrane]Collagen alpha-2(VI)chains[extracellularregion]PDGF A/B heterodimer[extracellularregion]PI3K [cytosol]PDGF:Phospho-PDGFreceptor dimer:SHP2[plasma membrane]Phospho-alpha-Phospho-betareceptor heterodimer[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]PDGF B homodimer[extracellularregion]Phospho- PDGFreceptor dimer[plasma membrane]PDGF:Phospho-PDGFreceptordimer:PLC-gamma[plasma membrane]Active PDGF dimers(AA, AB, BB)[extracellularregion]PDGF alpha receptor:PDGF dimers [plasmamembrane]PDGF B homodimer[extracellularregion]Phospho-alphareceptor homodimer[plasma membrane]GRB2:SOS1 [cytosol]PDGF A/B heterodimer[extracellularregion]PDGF B-chainprecursor dimer[endoplasmicreticulum lumen]CRK, CRKLPDGFA-2[extracellularregion]COL9A2[extracellularregion]PDGFB(82-241)[extracellularregion]Phospho PDGF alphareceptor:PDGF dimersCRK(2-304) [cytosol]RAF/MAP kinasecascadePI(3,4,5)P3PDGF:Phospho-PDGFreceptor dimerTHBS3 [extracellularregion]COL6A1[extracellularregion]PDGFA-1[extracellularregion]p-12Y-PDGFRB [plasmamembrane]PDGFA-1[extracellularregion]Active PDGF dimers(AA, AB, BB)PDGFA-2[extracellularregion]PIK3R1 [cytosol]PDGFA-1[extracellularregion]serine-typeendopeptidasesinvolved in novelPDGF processingPDGFB [extracellularregion]p-12Y-PDGFRB [plasmamembrane]PDGFA-2[extracellularregion]SRC-1 [plasmamembrane]PDGFB [extracellularregion]PDGFC-1(235-345)[extracellularregion]PDGFA-2 [Golgimembrane]PDGFB [extracellularregion]p21 RAS:GTPPDGF betareceptor:PDGF chainB homodimerPDGFB [extracellularregion]PDGFB [extracellularregion]p-11Y-PDGFRA [plasmamembrane]PDGFA-2 [endoplasmicreticulum lumen]PDGFB(82-241)[extracellularregion]PIK3R2 [cytosol]GDPPDGFB(82-241)[extracellularregion]Novel PDGF precursordimers (CC, DD)BCAR1Heparan sulfateN-acetyl-alpha-D-glucosaminide[extracellularregion]p-11Y-PDGFRA [plasmamembrane]COL9A3[extracellularregion]STAT5A [cytosol]ADP3x4Hyp-COL6A2[extracellularregion]3x4Hyp-COL6A1[extracellularregion]3x4Hyp-GlcGalHyl-COL6A1[extracellularregion]p-Y419-SRC-1 [plasmamembrane]PDGFB(82-241)[extracellularregion]PIK3CA [cytosol]PDGFB [extracellularregion]p-12Y-PDGFRB [plasmamembrane]PDGFB(82-241)[extracellularregion]RASA1 [cytosol]GalHyl-COL6A2[extracellularregion]PIK3CB [cytosol]5Hyl-COL6A1[extracellularregion]Phospho-betareceptorhomodimer:GAP5Hyl-COL6A2[extracellularregion]3x4Hyp-3Hyp-GlcGalHyl-COL6A1[extracellularregion]GTP [cytosol]PLCG1(2-1290)ADPCOL4A5(27-?)[extracellularregion]PI(4,5)P2PDGF:Phospho-PDGFreceptor dimer:Grb7Classical PDGFprecursor dimers(AA, AB, BB)PDGFA-1(1-211)[Golgi membrane]GRB2-1 [cytosol]PDGFD(1-370) [Golgimembrane]PDGFA-1[extracellularregion]PDGF:Phospho-PDGFreceptordimer:Grb2:Sos1PDGFA-1[extracellularregion]PIK3R2 [cytosol]PDGFA-1[extracellularregion]PDGFB(82-241)[extracellularregion]p-11Y-PDGFRA [plasmamembrane]PDGFB(82-241)[extracellularregion]PDGFRB [plasmamembrane]PDGFB(82-241)[extracellularregion]GRB2:SOS1p-11Y-PDGFRA [plasmamembrane]PDGFA-2[extracellularregion]GRB2-1 [cytosol]PDGFRA [plasmamembrane]PDGFA-2[extracellularregion]PDGFA-1[extracellularregion]PDGFA-1[extracellularregion]PDGFC-1 [Golgimembrane]GRB7 [cytosol]PDGFB(82-241)[extracellularregion]PDGFA-1[extracellularregion]Extracellular matrixligandsp-11Y-PDGFRA [plasmamembrane]Phospho PDGFalpha-betadimer:PDGF AB or BBdimers3x4Hyp-5Hyl-COL6A1[extracellularregion]ATPp-12Y-PDGFRB [plasmamembrane]GlcGalHyl-COL6A1[extracellularregion]PDGF:p-PDGFRdimer:p-PLCgammap-12Y-PDGFRB [plasmamembrane]p-11Y-PDGFRA [plasmamembrane]PDGFB(82-241)[extracellularregion]HRAS(1-186) [plasmamembrane]NRAS [plasmamembrane]PDGFB [extracellularregion]PDGF:PDGF receptordimerSRC-1PDGFB [extracellularregion]p-11Y-PDGFRA [plasmamembrane]KRAS(1-186) [plasmamembrane]PDGF alpha/beta:PDGFAB and BB dimersPDGFB(82-241)[extracellularregion]PDGFB [extracellularregion]PDGFRA [plasmamembrane]PDGFA-1[extracellularregion]p-12Y-PDGFRB [plasmamembrane]PI3KSOS1 [cytosol]PDGFB [extracellularregion]Phospho PDGF betareceptor: PDGF chainB homodimerPDGFB [extracellularregion]p-11Y-PDGFRA [plasmamembrane]STAT3 [cytosol]THBS2 [extracellularregion]p-11Y-PDGFRA [plasmamembrane]PDGFA-1[extracellularregion]PDGFB(82-241)[extracellularregion]NRAS [plasmamembrane]p-12Y-PDGFRB [plasmamembrane]PLCG1(2-1290)[plasma membrane]PDGFB(82-241)[extracellularregion]p-4Y-PLCG1 [plasmamembrane]PIK3CB [cytosol]PDGFA-2[extracellularregion]PDGF:Phospho-PDGFreceptor dimer:SHP2ATPp-12Y-PDGFRB [plasmamembrane]PDGF:Phospho-PDGFreceptor dimer:SrcGlcGalHyl-COL6A2[extracellularregion]PDGFB [extracellularregion]PDGF:phospho-PDGFreceptor dimer:STATPDGFB(82-241)[extracellularregion]PDGFA-2[extracellularregion]PDGFA-2[extracellularregion]3x4Hyp-3Hyp-5Hyl-COL6A1[extracellularregion]p-11Y-PDGFRA [plasmamembrane]Novel PDGF precursordimers (CC, DD)PDGFA-1[extracellularregion]PTPN11 [cytosol]Active PDGF dimers(CC, DD)COL4A2(184-?)[extracellularregion]GalHyl-COL6A1[extracellularregion]PDGFB(1-241) [Golgimembrane]PDGF:Phospho-PDGFreceptordimer:Crk:p130Cas:C3Gp-12Y-PDGFRB [plasmamembrane]3x4Hyp-GalHyl-COL6A1[extracellularregion]3x4Hyp-GlcGalHyl-COL6A2[extracellularregion]PDGFB(82-241)[extracellularregion]GRB7PDGFB [extracellularregion]Heparan sulfatealpha-D-glucosaminide[extracellularregion]COL6A2[extracellularregion]PDGFA-2[extracellularregion]PDGFA-2[extracellularregion]PDGFA-1[extracellularregion]p-12Y-PDGFRB [plasmamembrane]PDGFA-2[extracellularregion]PDGFD(1-370)[endoplasmicreticulum lumen]p-12Y-PDGFRB [plasmamembrane]ADPPDGFB [extracellularregion]3x4Hyp-3Hyp-COL6A1[extracellularregion]PDGFB(82-241)[extracellularregion]PDGFD(258-370)[extracellularregion]PDGFA-2[extracellularregion]DAG and IP3signaling3x4Hyp-3Hyp-5Hyl-COL6A2[extracellularregion]CRKL [cytosol]PDGFA-2[extracellularregion]ATPADPPDGFB(82-241)[extracellularregion]p-12Y-PDGFRB [plasmamembrane]PDGFB [extracellularregion]RAPGEF1p-12Y-PDGFRB [plasmamembrane]PDGF:Phospho-PDGFreceptor dimer:Crkp-11Y-PDGFRA [plasmamembrane]PDGFA-1[extracellularregion]PDGFB(82-241)[extracellularregion]p-4Y-PLCG1NCK1 [cytosol]PDGFA-2[extracellularregion]ADPPTPN11p-12Y-PDGFRB [plasmamembrane]STAT1 [cytosol]NCKPDGFA-2[extracellularregion]PDGF:Phospho-PDGFreceptordimer:phospho-Src3x4Hyp-5Hyl-COL6A2[extracellularregion]PDGFB(1-241) [Golgimembrane]p-12Y-PDGFRB [plasmamembrane]3x4Hyp-GalHyl-COL6A2[extracellularregion]PDGFB [extracellularregion]PDGFB [extracellularregion]PDGFRA [plasmamembrane]SPP1(17-?)[extracellularregion]PDGFA-1(1-211)[endoplasmicreticulum lumen]ATPPDGFB(82-241)[extracellularregion]STAT5B [cytosol]THBS1 [extracellularregion]PDGF A and B chainswith retention motifPDGFB [extracellularregion]COL4A1(173-1669)[extracellularregion]Cleaved novel PDGFfragmentsp-11Y-PDGFRA [plasmamembrane]PDGFB [extracellularregion]PDGFB(82-241)[extracellularregion]p-11Y-PDGFRA [plasmamembrane]PDGFB [extracellularregion]GDP [cytosol]PDGFD(1-370) [Golgimembrane]PDGFA-2 [Golgimembrane]3x4Hyp-3Hyp-GalHyl-COL6A2[extracellularregion]PDGFC-1 [endoplasmicreticulum lumen]CRKL [cytosol]GTP3x4Hyp-3Hyp-COL6A2[extracellularregion]PDGFRB [plasmamembrane]p-11Y-PDGFRA [plasmamembrane]Cleaved classicalPDGF peptides3x4Hyp-3Hyp-GlcGalHyl-COL6A2[extracellularregion]PIK3R1 [cytosol]CRK(2-304) [cytosol]PDGFB(82-241)[extracellularregion]PDGFB(1-241)[endoplasmicreticulum lumen]PDGFA-2[extracellularregion]ATPPDGFD(19-370)[extracellularregion]p21 RAS:GDPPDGFA-1[extracellularregion]p-11Y-PDGFRA [plasmamembrane]PDGFA-1[extracellularregion]KRAS(1-186) [plasmamembrane]PDGFA-1[extracellularregion]PDGFA-2[extracellularregion]SOS1 [cytosol]RAPGEF1 [cytosol]STAT6 [cytosol]NCK2 [cytosol]PDGF receptormonomerPDGFC-1(23-345)[extracellularregion]PDGFA-1[extracellularregion]PDGF:Phospho-PDGFRreceptor dimer:NckPDGF precursordimers (AA, BB,A/B, CC, DD)PDGF:Phospho-PDGFreceptordimer:PLC-gammaHRAS(1-186) [plasmamembrane]THBS4 [extracellularregion]PDGFB(82-241)[extracellularregion]PDGF alpha receptor:PDGF dimers3x4Hyp-3Hyp-GalHyl-COL6A1[extracellularregion]COL4A4(39-?)[extracellularregion]PDGFA-1(1-211)[Golgi membrane]PDGFA-2[extracellularregion]PDGF precursordimers (AA, BB, A/B,CC, DD)COL9A1[extracellularregion]RASA1PDGFB [extracellularregion]COL4A3(29-1670)[extracellularregion]PDGFA-2[extracellularregion]PIP3 activates AKTsignalingSTAT family membersPDGFC-1 [Golgimembrane]PIK3CA [cytosol]PDGFB(82-241)[extracellularregion]PDGF:Phospho-PDGFreceptor dimer:PI3KFURINp-12Y-PDGFRB [plasmamembrane]PDGF A and Bchains:ECM complexPDGFB [extracellularregion]PDGFRB [plasmamembrane]BCAR1 [cytosol]1012, 2115


Description

Platelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary endothelial cells and neurons.The PDGF family of growth factors is composed of four different polypeptide chains encoded by four different genes. The classical PDGF chains, PDGF-A and PDGF-B, and more recently discovered PDGF-C and PDGF-D. The four PDGF chains assemble into disulphide-bonded dimers via homo- or heterodimerization, and five different dimeric isoforms have been described so far; PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD. It is notable that no heterodimers involving PDGF-C and PDGF-D chains have been described. PDGF exerts its effects by binding to, and activating, two protein tyrosine kinase (PTK) receptors, alpha and beta. These receptors dimerize and undergo autophosphorylation. The phosphorylation sites then attract downstream effectors to transduct the signal into the cell.Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=186797

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  6. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
  7. Rönnstrand L, Mori S, Arridsson AK, Eriksson A, Wernstedt C, Hellman U, Claesson-Welsh L, Heldin CH.; ''Identification of two C-terminal autophosphorylation sites in the PDGF beta-receptor: involvement in the interaction with phospholipase C-gamma.''; PubMed Europe PMC Scholia
  8. Sun T, Aceto N, Meerbrey KL, Kessler JD, Zhou C, Migliaccio I, Nguyen DX, Pavlova NN, Botero M, Huang J, Bernardi RJ, Schmitt E, Hu G, Li MZ, Dephoure N, Gygi SP, Rao M, Creighton CJ, Hilsenbeck SG, Shaw CA, Muzny D, Gibbs RA, Wheeler DA, Osborne CK, Schiff R, Bentires-Alj M, Elledge SJ, Westbrook TF.; ''Activation of multiple proto-oncogenic tyrosine kinases in breast cancer via loss of the PTPN12 phosphatase.''; PubMed Europe PMC Scholia
  9. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
  10. Somasundaram R, Schuppan D.; ''Type I, II, III, IV, V, and VI collagens serve as extracellular ligands for the isoforms of platelet-derived growth factor (AA, BB, and AB).''; PubMed Europe PMC Scholia
  11. Lechleider RJ, Sugimoto S, Bennett AM, Kashishian AS, Cooper JA, Shoelson SE, Walsh CT, Neel BG.; ''Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor.''; PubMed Europe PMC Scholia
  12. Nishimura R, Li W, Kashishian A, Mondino A, Zhou M, Cooper J, Schlessinger J.; ''Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.''; PubMed Europe PMC Scholia
  13. Satoh T, Fantl WJ, Escobedo JA, Williams LT, Kaziro Y.; ''Platelet-derived growth factor receptor mediates activation of ras through different signaling pathways in different cell types.''; PubMed Europe PMC Scholia
  14. Heldin CH, Westermark B.; ''Mechanism of action and in vivo role of platelet-derived growth factor.''; PubMed Europe PMC Scholia
  15. Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, Bar-Sagi D.; ''Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.''; PubMed Europe PMC Scholia
  16. Hogg PJ, Hotchkiss KA, Jiménez BM, Stathakis P, Chesterman CN.; ''Interaction of platelet-derived growth factor with thrombospondin 1.''; PubMed Europe PMC Scholia
  17. Fredriksson L, Li H, Eriksson U.; ''The PDGF family: four gene products form five dimeric isoforms.''; PubMed Europe PMC Scholia
  18. Gelderloos JA, Rosenkranz S, Bazenet C, Kazlauskas A.; ''A role for Src in signal relay by the platelet-derived growth factor alpha receptor.''; PubMed Europe PMC Scholia
  19. Kazlauskas A, Kashishian A, Cooper JA, Valius M.; ''GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit.''; PubMed Europe PMC Scholia
  20. Leduc R, Molloy SS, Thorne BA, Thomas G.; ''Activation of human furin precursor processing endoprotease occurs by an intramolecular autoproteolytic cleavage.''; PubMed Europe PMC Scholia
  21. Roberts PJ, Der CJ.; ''Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.''; PubMed Europe PMC Scholia
  22. Fantl WJ, Escobedo JA, Martin GA, Turck CW, del Rosario M, McCormick F, Williams LT.; ''Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways.''; PubMed Europe PMC Scholia
  23. Brown MD, Sacks DB.; ''Protein scaffolds in MAP kinase signalling.''; PubMed Europe PMC Scholia
  24. Raines EW, Lane TF, Iruela-Arispe ML, Ross R, Sage EH.; ''The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors.''; PubMed Europe PMC Scholia
  25. Heldin CH, Ostman A, Rönnstrand L.; ''Signal transduction via platelet-derived growth factor receptors.''; PubMed Europe PMC Scholia
  26. Ostman A, Thyberg J, Westermark B, Heldin CH.; ''PDGF-AA and PDGF-BB biosynthesis: proprotein processing in the Golgi complex and lysosomal degradation of PDGF-BB retained intracellularly.''; PubMed Europe PMC Scholia
  27. Stover DR, Furet P, Lydon NB.; ''Modulation of the SH2 binding specificity and kinase activity of Src by tyrosine phosphorylation within its SH2 domain.''; PubMed Europe PMC Scholia
  28. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
  29. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
  30. Meisenhelder J, Suh PG, Rhee SG, Hunter T.; ''Phospholipase C-gamma is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro.''; PubMed Europe PMC Scholia
  31. Vignais ML, Sadowski HB, Watling D, Rogers NC, Gilman M.; ''Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins.''; PubMed Europe PMC Scholia
  32. Patterson RL, van Rossum DB, Nikolaidis N, Gill DL, Snyder SH.; ''Phospholipase C-gamma: diverse roles in receptor-mediated calcium signaling.''; PubMed Europe PMC Scholia
  33. Mori S, Rönnstrand L, Yokote K, Engström A, Courtneidge SA, Claesson-Welsh L, Heldin CH.; ''Identification of two juxtamembrane autophosphorylation sites in the PDGF beta-receptor; involvement in the interaction with Src family tyrosine kinases.''; PubMed Europe PMC Scholia
  34. Arvidsson AK, Rupp E, Nånberg E, Downward J, Rönnstrand L, Wennström S, Schlessinger J, Heldin CH, Claesson-Welsh L.; ''Tyr-716 in the platelet-derived growth factor beta-receptor kinase insert is involved in GRB2 binding and Ras activation.''; PubMed Europe PMC Scholia
  35. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA.; ''Mutations of the BRAF gene in human cancer.''; PubMed Europe PMC Scholia
  36. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
  37. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
  38. Valgeirsdóttir S, Paukku K, Silvennoinen O, Heldin CH, Claesson-Welsh L.; ''Activation of Stat5 by platelet-derived growth factor (PDGF) is dependent on phosphorylation sites in PDGF beta-receptor juxtamembrane and kinase insert domains.''; PubMed Europe PMC Scholia
  39. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
  40. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
  41. Coughlin SR, Escobedo JA, Williams LT.; ''Role of phosphatidylinositol kinase in PDGF receptor signal transduction.''; PubMed Europe PMC Scholia
  42. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
  43. Carpenter G, Ji Q.; ''Phospholipase C-gamma as a signal-transducing element.''; PubMed Europe PMC Scholia
  44. McKay MM, Morrison DK.; ''Integrating signals from RTKs to ERK/MAPK.''; PubMed Europe PMC Scholia
  45. Fukumoto T, Kubota Y, Kitanaka A, Yamaoka G, Ohara-Waki F, Imataki O, Ohnishi H, Ishida T, Tanaka T.; ''Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
101493view11:36, 1 November 2018ReactomeTeamreactome version 66
101030view21:16, 31 October 2018ReactomeTeamreactome version 65
100563view19:50, 31 October 2018ReactomeTeamreactome version 64
100111view16:35, 31 October 2018ReactomeTeamreactome version 63
99661view15:06, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99261view12:45, 31 October 2018ReactomeTeamreactome version 62
93838view13:40, 16 August 2017ReactomeTeamreactome version 61
93393view11:22, 9 August 2017ReactomeTeamreactome version 61
86479view09:19, 11 July 2016ReactomeTeamreactome version 56
83084view09:55, 18 November 2015ReactomeTeamVersion54
81405view12:56, 21 August 2015ReactomeTeamVersion53
76874view08:14, 17 July 2014ReactomeTeamFixed remaining interactions
76579view11:56, 16 July 2014ReactomeTeamFixed remaining interactions
75912view09:56, 11 June 2014ReactomeTeamRe-fixing comment source
75612view10:47, 10 June 2014ReactomeTeamReactome 48 Update
74967view13:48, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74611view08:39, 30 April 2014ReactomeTeamReactome46
45212view17:24, 7 October 2011KhanspersOntology Term : 'PDGF signaling pathway' added !
42132view21:59, 4 March 2011MaintBotAutomatic update
39942view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
3x4Hyp-3Hyp-5Hyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GalHyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GalHyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GlcGalHyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GlcGalHyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-5Hyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-5Hyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-GalHyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-GalHyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-GlcGalHyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-GlcGalHyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
5Hyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
5Hyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Active PDGF dimers (AA, AB, BB)ComplexREACT_17845 (Reactome)
Active PDGF dimers (CC, DD)ComplexREACT_17802 (Reactome)
BCAR1 [cytosol]ProteinP56945 (Uniprot-TrEMBL)
BCAR1ProteinP56945 (Uniprot-TrEMBL)
COL4A1(173-1669)

[extracellular

region]		ProteinP02462 (Uniprot-TrEMBL)
COL4A2(184-?)

[extracellular

region]		ProteinP08572 (Uniprot-TrEMBL)
COL4A3(29-1670)

[extracellular

region]		ProteinQ01955 (Uniprot-TrEMBL)
COL4A4(39-?)

[extracellular

region]		ProteinP53420 (Uniprot-TrEMBL)
COL4A5(27-?)

[extracellular

region]		ProteinP29400 (Uniprot-TrEMBL)
COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
COL9A1

[extracellular

region]		ProteinP20849 (Uniprot-TrEMBL)
COL9A2

[extracellular

region]		ProteinQ14055 (Uniprot-TrEMBL)
COL9A3

[extracellular

region]		ProteinQ14050 (Uniprot-TrEMBL)
CRK(2-304) [cytosol]ProteinP46108 (Uniprot-TrEMBL)
CRK, CRKLProteinREACT_17492 (Reactome)
CRKL [cytosol]ProteinP46109 (Uniprot-TrEMBL)
Classical PDGF

precursor dimers

(AA, AB, BB)		ComplexREACT_17671 (Reactome)
Cleaved classical PDGF peptidesProteinREACT_17262 (Reactome)
Cleaved novel PDGF fragmentsProteinREACT_18041 (Reactome)
DAG and IP3 signalingPathwayWP2688 (WikiPathways) This pathway describes the generation of DAG and IP3 by the PLCgamma-mediated hydrolysis of PIP2 and the subsequent downstream signaling events.
Extracellular matrix ligandsProteinREACT_17129 (Reactome)
FURINProteinP09958 (Uniprot-TrEMBL)
GDP [cytosol]MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRB2-1 [cytosol]ProteinP62993-1 (Uniprot-TrEMBL)
GRB2:SOS1ComplexREACT_4435 (Reactome)
GRB7 [cytosol]ProteinQ14451 (Uniprot-TrEMBL)
GRB7ProteinQ14451 (Uniprot-TrEMBL)
GTP [cytosol]MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
GalHyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
GalHyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
GlcGalHyl-COL6A1

[extracellular

region]		ProteinP12109 (Uniprot-TrEMBL)
GlcGalHyl-COL6A2

[extracellular

region]		ProteinP12110 (Uniprot-TrEMBL)
HRAS(1-186) [plasma membrane]ProteinP01112 (Uniprot-TrEMBL)
Heparan sulfate

N-acetyl-alpha-D-glucosaminide [extracellular

region]		MetaboliteCHEBI:17421 (ChEBI)
Heparan sulfate

alpha-D-glucosaminide [extracellular

region]		MetaboliteCHEBI:18137 (ChEBI)
KRAS(1-186) [plasma membrane]ProteinP01116 (Uniprot-TrEMBL)
NCK1 [cytosol]ProteinP16333 (Uniprot-TrEMBL)
NCK2 [cytosol]ProteinO43639 (Uniprot-TrEMBL)
NCKProteinREACT_17190 (Reactome)
NRAS [plasma membrane]ProteinP01111 (Uniprot-TrEMBL)
Novel PDGF precursor dimers (CC, DD)ComplexREACT_17079 (Reactome)
Novel PDGF precursor dimers (CC, DD)ComplexREACT_17162 (Reactome)
PDGF A and B chains:ECM complexComplexREACT_17710 (Reactome)
PDGF A and B chains with retention motifProteinREACT_17714 (Reactome)
PDGF alpha receptor: PDGF dimersComplexREACT_17393 (Reactome)
PDGF alpha/beta:PDGF AB and BB dimersComplexREACT_17544 (Reactome)
PDGF beta

receptor:PDGF chain

B homodimer		ComplexREACT_17457 (Reactome)
PDGF precursor

dimers (AA, BB,

A/B, CC, DD)		ComplexREACT_17541 (Reactome)
PDGF precursor

dimers (AA, BB, A/B,

CC, DD)		ComplexREACT_17912 (Reactome)
PDGF receptor monomerProteinREACT_18211 (Reactome)
PDGF:PDGF receptor dimerComplexREACT_18025 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:Crk:p130Cas:C3G		ComplexREACT_17351 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:Grb2:Sos1		ComplexREACT_18248 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:PLC-gamma		ComplexREACT_17327 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:phospho-Src		ComplexREACT_17206 (Reactome)
PDGF:Phospho-PDGF receptor dimer:CrkComplexREACT_17941 (Reactome)
PDGF:Phospho-PDGF receptor dimer:Grb7ComplexREACT_17607 (Reactome)
PDGF:Phospho-PDGF receptor dimer:PI3KComplexREACT_17825 (Reactome)
PDGF:Phospho-PDGF receptor dimer:SHP2ComplexREACT_17654 (Reactome)
PDGF:Phospho-PDGF receptor dimer:SrcComplexREACT_18132 (Reactome)
PDGF:Phospho-PDGF receptor dimerComplexREACT_17756 (Reactome)
PDGF:Phospho-PDGFR receptor dimer:NckComplexREACT_17490 (Reactome)
PDGF:p-PDGFR dimer:p-PLCgammaComplexREACT_111673 (Reactome)
PDGF:phospho-PDGF receptor dimer:STATComplexREACT_17883 (Reactome)
PDGFA-1

[extracellular

region]		ProteinP04085-1 (Uniprot-TrEMBL)
PDGFA-1(1-211) [Golgi membrane]ProteinP04085-1 (Uniprot-TrEMBL)
PDGFA-1(1-211)

[endoplasmic

reticulum lumen]		ProteinP04085-1 (Uniprot-TrEMBL)
PDGFA-2

[extracellular

region]		ProteinP04085-2 (Uniprot-TrEMBL)
PDGFA-2 [Golgi membrane]ProteinP04085-2 (Uniprot-TrEMBL)
PDGFA-2 [endoplasmic reticulum lumen]ProteinP04085-2 (Uniprot-TrEMBL)
PDGFB [extracellular region]ProteinP01127 (Uniprot-TrEMBL)
PDGFB(1-241)

[endoplasmic

reticulum lumen]		ProteinP01127 (Uniprot-TrEMBL)
PDGFB(1-241) [Golgi membrane]ProteinP01127 (Uniprot-TrEMBL)
PDGFB(82-241)

[extracellular

region]		ProteinP01127 (Uniprot-TrEMBL)
PDGFC-1 [Golgi membrane]ProteinQ9NRA1-1 (Uniprot-TrEMBL)
PDGFC-1 [endoplasmic reticulum lumen]ProteinQ9NRA1-1 (Uniprot-TrEMBL)
PDGFC-1(23-345)

[extracellular

region]		ProteinQ9NRA1-1 (Uniprot-TrEMBL)
PDGFC-1(235-345)

[extracellular

region]		ProteinQ9NRA1-1 (Uniprot-TrEMBL)
PDGFD(1-370)

[endoplasmic

reticulum lumen]		ProteinQ9GZP0 (Uniprot-TrEMBL)
PDGFD(1-370) [Golgi membrane]ProteinQ9GZP0 (Uniprot-TrEMBL)
PDGFD(19-370)

[extracellular

region]		ProteinQ9GZP0 (Uniprot-TrEMBL)
PDGFD(258-370)

[extracellular

region]		ProteinQ9GZP0 (Uniprot-TrEMBL)
PDGFRA [plasma membrane]ProteinP16234 (Uniprot-TrEMBL)
PDGFRB [plasma membrane]ProteinP09619 (Uniprot-TrEMBL)
PI(3,4,5)P3MetaboliteCHEBI:16618 (ChEBI)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PI3KComplexREACT_4240 (Reactome)
PIK3CA [cytosol]ProteinP42336 (Uniprot-TrEMBL)
PIK3CB [cytosol]ProteinP42338 (Uniprot-TrEMBL)
PIK3R1 [cytosol]ProteinP27986 (Uniprot-TrEMBL)
PIK3R2 [cytosol]ProteinO00459 (Uniprot-TrEMBL)
PIP3 activates AKT signalingPathwayWP2653 (WikiPathways) Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PLCG1(2-1290) [plasma membrane]ProteinP19174 (Uniprot-TrEMBL)
PLCG1(2-1290)ProteinP19174 (Uniprot-TrEMBL)
PTPN11 [cytosol]ProteinQ06124 (Uniprot-TrEMBL)
PTPN11ProteinQ06124 (Uniprot-TrEMBL)
Phospho PDGF

alpha-beta dimer:PDGF AB or BB

dimers		ComplexREACT_17875 (Reactome)
Phospho PDGF alpha receptor:PDGF dimersComplexREACT_17261 (Reactome)
Phospho PDGF beta

receptor: PDGF chain

B homodimer		ComplexREACT_17403 (Reactome)
Phospho-beta

receptor

homodimer:GAP		ComplexREACT_17783 (Reactome)
RAF/MAP kinase cascadePathwayWP2735 (WikiPathways) The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
RAPGEF1 [cytosol]ProteinQ13905 (Uniprot-TrEMBL)
RAPGEF1ProteinQ13905 (Uniprot-TrEMBL)
RASA1 [cytosol]ProteinP20936 (Uniprot-TrEMBL)
RASA1ProteinP20936 (Uniprot-TrEMBL)
SOS1 [cytosol]ProteinQ07889 (Uniprot-TrEMBL)
SPP1(17-?)

[extracellular

region]		ProteinP10451 (Uniprot-TrEMBL)
SRC-1 [plasma membrane]ProteinP12931-1 (Uniprot-TrEMBL)
SRC-1ProteinP12931-1 (Uniprot-TrEMBL)
STAT family membersProteinREACT_17706 (Reactome)
STAT1 [cytosol]ProteinP42224 (Uniprot-TrEMBL)
STAT3 [cytosol]ProteinP40763 (Uniprot-TrEMBL)
STAT5A [cytosol]ProteinP42229 (Uniprot-TrEMBL)
STAT5B [cytosol]ProteinP51692 (Uniprot-TrEMBL)
STAT6 [cytosol]ProteinP42226 (Uniprot-TrEMBL)
THBS1 [extracellular region]ProteinP07996 (Uniprot-TrEMBL)
THBS2 [extracellular region]ProteinP35442 (Uniprot-TrEMBL)
THBS3 [extracellular region]ProteinP49746 (Uniprot-TrEMBL)
THBS4 [extracellular region]ProteinP35443 (Uniprot-TrEMBL)
p-11Y-PDGFRA [plasma membrane]ProteinP16234 (Uniprot-TrEMBL)
p-12Y-PDGFRB [plasma membrane]ProteinP09619 (Uniprot-TrEMBL)
p-4Y-PLCG1 [plasma membrane]ProteinP19174 (Uniprot-TrEMBL)
p-4Y-PLCG1ProteinP19174 (Uniprot-TrEMBL)
p-Y419-SRC-1 [plasma membrane]ProteinP12931-1 (Uniprot-TrEMBL)
p21 RAS:GDPComplexREACT_2657 (Reactome)
p21 RAS:GTPComplexREACT_4782 (Reactome)
serine-type

endopeptidases involved in novel

PDGF processing		REACT_17837 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_16877 (Reactome)
ADPArrowREACT_16926 (Reactome)
ADPArrowREACT_16991 (Reactome)
ADPArrowREACT_16993 (Reactome)
ADPArrowREACT_17034 (Reactome)
ATPREACT_16877 (Reactome)
ATPREACT_16926 (Reactome)
ATPREACT_16991 (Reactome)
ATPREACT_16993 (Reactome)
ATPREACT_17034 (Reactome)
Active PDGF dimers (AA, AB, BB)ArrowREACT_17059 (Reactome)
Active PDGF dimers (AA, AB, BB)REACT_16905 (Reactome)
Active PDGF dimers (CC, DD)ArrowREACT_16891 (Reactome)
BCAR1REACT_16951 (Reactome)
CRK, CRKLREACT_16940 (Reactome)
Classical PDGF

precursor dimers

(AA, AB, BB)		REACT_17059 (Reactome)
Cleaved classical PDGF peptidesArrowREACT_17059 (Reactome)
Cleaved novel PDGF fragmentsArrowREACT_16891 (Reactome)
Extracellular matrix ligandsREACT_16880 (Reactome)
FURINmim-catalysisREACT_17059 (Reactome)
GDPArrowREACT_16923 (Reactome)
GRB2:SOS1REACT_16901 (Reactome)
GRB7REACT_17063 (Reactome)
GTPREACT_16923 (Reactome)
NCKREACT_16997 (Reactome)
Novel PDGF precursor dimers (CC, DD)ArrowREACT_17022 (Reactome)
Novel PDGF precursor dimers (CC, DD)REACT_16891 (Reactome)
Novel PDGF precursor dimers (CC, DD)REACT_17022 (Reactome)
PDGF A and B chains:ECM complexArrowREACT_16880 (Reactome)
PDGF A and B chains with retention motifREACT_16880 (Reactome)
PDGF alpha receptor: PDGF dimersREACT_16993 (Reactome)
PDGF alpha receptor: PDGF dimersmim-catalysisREACT_16993 (Reactome)
PDGF alpha/beta:PDGF AB and BB dimersREACT_17034 (Reactome)
PDGF alpha/beta:PDGF AB and BB dimersmim-catalysisREACT_17034 (Reactome)
PDGF beta

receptor:PDGF chain

B homodimer		REACT_16926 (Reactome)
PDGF beta

receptor:PDGF chain

B homodimer		mim-catalysisREACT_16926 (Reactome)
PDGF precursor

dimers (AA, BB,

A/B, CC, DD)		REACT_17051 (Reactome)
PDGF precursor

dimers (AA, BB, A/B,

CC, DD)		ArrowREACT_17051 (Reactome)
PDGF receptor monomerREACT_16905 (Reactome)
PDGF:PDGF receptor dimerArrowREACT_16905 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:Crk:p130Cas:C3G		ArrowREACT_16951 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:Grb2:Sos1		ArrowREACT_16901 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:Grb2:Sos1		mim-catalysisREACT_16923 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:PLC-gamma		ArrowREACT_16998 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:PLC-gamma		REACT_111134 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:PLC-gamma		mim-catalysisREACT_111134 (Reactome)
PDGF:Phospho-PDGF

receptor

dimer:phospho-Src		ArrowREACT_16991 (Reactome)
PDGF:Phospho-PDGF receptor dimer:CrkArrowREACT_16940 (Reactome)
PDGF:Phospho-PDGF receptor dimer:CrkREACT_16951 (Reactome)
PDGF:Phospho-PDGF receptor dimer:Grb7ArrowREACT_17063 (Reactome)
PDGF:Phospho-PDGF receptor dimer:PI3KArrowREACT_17052 (Reactome)
PDGF:Phospho-PDGF receptor dimer:PI3Kmim-catalysisREACT_16877 (Reactome)
PDGF:Phospho-PDGF receptor dimer:SHP2ArrowREACT_16960 (Reactome)
PDGF:Phospho-PDGF receptor dimer:SrcArrowREACT_17048 (Reactome)
PDGF:Phospho-PDGF receptor dimer:SrcREACT_16991 (Reactome)
PDGF:Phospho-PDGF receptor dimerArrowREACT_111066 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_16901 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_16940 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_16960 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_16982 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_16997 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_16998 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_17048 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_17052 (Reactome)
PDGF:Phospho-PDGF receptor dimerREACT_17063 (Reactome)
PDGF:Phospho-PDGFR receptor dimer:NckArrowREACT_16997 (Reactome)
PDGF:p-PDGFR dimer:p-PLCgammaArrowREACT_111134 (Reactome)
PDGF:p-PDGFR dimer:p-PLCgammaREACT_111066 (Reactome)
PDGF:phospho-PDGF receptor dimer:STATArrowREACT_16982 (Reactome)
PI(3,4,5)P3ArrowREACT_16877 (Reactome)
PI(4,5)P2REACT_16877 (Reactome)
PI3KREACT_17052 (Reactome)
PLCG1(2-1290)REACT_16998 (Reactome)
PTPN11REACT_16960 (Reactome)
Phospho PDGF

alpha-beta dimer:PDGF AB or BB

dimers		ArrowREACT_17034 (Reactome)
Phospho PDGF alpha receptor:PDGF dimersArrowREACT_16993 (Reactome)
Phospho PDGF beta

receptor: PDGF chain

B homodimer		ArrowREACT_16926 (Reactome)
Phospho PDGF beta

receptor: PDGF chain

B homodimer		REACT_16950 (Reactome)
Phospho-beta

receptor

homodimer:GAP		ArrowREACT_16950 (Reactome)
RAPGEF1REACT_16951 (Reactome)
RASA1REACT_16950 (Reactome)
REACT_111066 (Reactome) Once phosphorylated, PLCgamma dissociates from the receptor. The active enzyme promotes intracelllular signaling by catalysing the hydrolysis of PIP2 to generate the second messengers IP3 and DAG.
REACT_111134 (Reactome) The activated PDGF receptor phosphorylates PLCgamma on tyrosine residues 472,771,783 and 1254, activating the enzyme.
REACT_16877 (Reactome) PI3K's preferred substrate is phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] which is phosphorylated to the trisphosphate [PI(3,4,5)P3]. PI3-kinase and its products have been found to be of importance in PDGF-stimulated actin reorganization, and directed cell movement, as well as in the stimulation of cell growth and inhibition of apoptosis.
REACT_16880 (Reactome) The long splice version of the PDGF-A chain as well as the COOH-terminal part of the PDGF-B precursor contain C-terminal protein motifs that confer retention of the secreted factors. In both the PDGF A- and B-chains, exon 6 encodes a basic sequence that mediates interaction with components of the extracellular matrix. PDGF binds to various types of collagens, thrombospondin and osteopontin; however, the major component of the matrix involved in PDGF binding is likely to be haparan sulphate. The negatively charged sulfate groups on the disaccharide building blocks of heparan sulfate (HS) polysaccharide chains provide binding sites for positively charged amino acid sequence motifs.
The precursor of the B-chain may be retained in the matrix; after maturation when the COOH-terminal retention sequence has been cleaved off, the molecule may become more diffusible.
REACT_16891 (Reactome) During the extracellular proteolytic activation of PDGF-C and PDGF-D chains, the CUB domains is removed and plasmin protease has been shown to proteolytically cleave within the hinge regions, and thus releasing the corresponding growth factor domains. In addition the protease tissue-type plasminogen activator (tPA) is also involved in the activation of PDGF-CC but not able to cleave and activate PDGF-DD.
REACT_16901 (Reactome) Grb2 is an adaptor molecule containing one SH2 domain and two SH3 domains. The SH2 domain of Grb2 binds directly to autophosphorylated PDGF receptors and with its SH3 domain it forms a complex with Sos1. The binding of Grb2/Sos1 to the PDGF receptor juxtaposes the complex towards Ras molecules leading to Ras activation. Ras is implicated in the MAP kinase cascade, a pathway in cell growth stimulation, migration and differentiation.

REACT_16905 (Reactome) PDGF dimer binds two receptors simultaneously. The receptors dimerise on binding and this is key to receptor autophosphorylation.
REACT_16923 (Reactome) SOS is the guanine nucleotide exchange factor (GEF) for Ras. SOS activates Ras nucleotide exchange from the inactive form (bound to GDP) to an active form (bound to GTP).

REACT_16926 (Reactome) Receptor dimerisation is key event in PDGF receptor activation. The intracellular parts of the receptors are juxtaposed which allows trans-phosphorylation between the two receptors in the complex.
The autophosphorylation site Y857 located inside the kinase domain of beta-receptor is important for activation of the kinase. This tyrosine is conserved in the alpha-receptor (Y849 ) and in almost all other tyrosine kinase receptors. The other known autophosphorylation sites are localized outside the kinase domains of the alpha- and beta- receptors ; 11 out of 15 tyrosine residues in the intracellular, non-catalytic part of the beta-receptor are autophosphorylation sites
REACT_16940 (Reactome) Crk family of adaptor molecules consists of CrkI with one SH2 and one SH3 domains and CrkII and CrkL with one SH2 and two SH3 domains each. They bind to Tyr762 of the PDGF alpha-receptor and represent the only known SH2-domain containing molecule which binds with significantly higher affinity to the alpha-receptor than to the beta-receptor.
REACT_16950 (Reactome) GTPase-activating protein (GAP) has two SH2 domains which bind only to PDGF beta-receptors on Tyr771. GAP does not bind the alpha-receptor. GAP converts Ras-GTP to Ras-GDP, deactivating Ras.
REACT_16951 (Reactome) The presence of both SH2 and SH3 domains in Crk proteins is of crucial importance for their function as adaptor molecules. Crk forms complex with Cas, an SH3 domain-containing docking protein which has been shown to be phosphorylated after PDGF-stimulation of cells, and C3G, a nucleotide exchange protein which has been linked to the activation of JNK.
REACT_16960 (Reactome) Protein-tyrosine phosphatase 2C (SHP2) is ubiquitously expressed and has two SH2 domains, both of which need to be bound to phosphorylated tyrosine residues for full activation of catalytic activity. SHP-2 binds with high affinity to Tyr 1009 of the PDGF beta-receptor and with lower affinity to Tyr 763; it also binds to the alpha-receptor and Tyr 720 in the interkinase domain has been implicated in this binding.
The phosphatase is able to dephosphorylate autophosphorylated PDGF receptors and substrates for PDGF receptors so SHP2 can be thought of as a negative regulator of signaling from PDGF receptors. SHP2 may be involved in positive signaling by binding Grb2/Sos1 and dephosphorylating the COOH-terminal tyrosine of Src, factors important for Src activation.
REACT_16982 (Reactome) Among the seven members of the Stat family, Stat1, Stat3, Stat5 alpha and -beta, and Stat6 have been shown to bind to the activated PDGF beta-receptor and to be phosphorylated after PDGF stimulation; binding also occurs to the alpha-receptor, albeit only weakly.
REACT_16991 (Reactome) Activation of Src kinases involves displacement of Tyr527 from the SH2 domain and phosphorylation of other tyrosine residues in the kinase domain. Src activation appears to be important for the mitogenic response of PDGF.
REACT_16993 (Reactome) Receptor dimerisation is key event in PDGF receptor activation. The intracellular parts of the receptors are juxtaposed which allows trans-phosphorylation between the two receptors in the complex.
The autophosphorylation site Y857 located inside the kinase domain of beta-receptor is important for activation of the kinase. This tyrosine is conserved in the alpha-receptor (Y849 ) and in almost all other tyrosine kinase receptors. The other known autophosphorylation sites are localized outside the kinase domains of the alpha- and beta- receptors ; 11 out of 15 tyrosine residues in the intracellular, non-catalytic part of the beta-receptor are autophosphorylation sites
REACT_16997 (Reactome) Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains. With its SH2 doamin Nck interacts with Tyr571 of the PDGF beta-receptor and it also interacts with the alpha-receptor, but the sites of interaction has not been determined. Nck is involved in the activation of the JNK serine/threonine kinase through interaction with the serine/threonine kinases PAK1 and NIK.
REACT_16998 (Reactome) PLC-gamma 1 has been shown to bind to phosphorylated Tyr 1021 of the PDGF beta-receptor with high affinity and to Tyr 1009 with low affinity. In the alpha-receptor, Tyr 988 and Tyr 1018 bind PLC-gamma1. Association of PLC-gamma1 with the activated PDGF receptor has been shown to be necessary for its activation.

REACT_17022 (Reactome) Novel PDGFs both PDGF-CC and PDGF-DD dimers are secreted as latent factors without removal of the N-terminal CUB domain. These require further activation by extracellular proteolysis.
REACT_17034 (Reactome) Receptor dimerisation is key event in PDGF receptor activation. The intracellular parts of the receptors are juxtaposed which allows trans-phosphorylation between the two receptors in the complex.
The autophosphorylation site Y857 located inside the kinase domain of beta-receptor is important for activation of the kinase. This tyrosine is conserved in the alpha-receptor (Y849 ) and in almost all other tyrosine kinase receptors. The other known autophosphorylation sites are localized outside the kinase domains of the alpha- and beta- receptors ; 11 out of 15 tyrosine residues in the intracellular, non-catalytic part of the beta-receptor are autophosphorylation sites
REACT_17048 (Reactome) The Src family of tyrosine kinases are characterized by a SH3 and a SH2 domain in addition to the kinase domain.Src is activated when the SH2 domain binds to autophosphorylation sites on PDGF receptors (Tyr579 and 581 in the beta-receptor, Tyr572 and 574 in the alpha receptor), in conjuction with dephosporylation of the COOH-terminal phosphorylated tyrosine 527.
REACT_17051 (Reactome) All the newly synthesized PDGF chains are dimerized in the ER and thereafter transferred to the Golgi complex for proteolytic processing. The four PDGF chains assemble into disulphide-bonded dimers via homo- or heterodimerization, and five different dimeric isoforms have been described so far; PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD.
REACT_17052 (Reactome) Phosphatidylinositol 3'-kinases (PI3Ks) are a family of enzymes which can phosphorylate phosphoinositides. These bind to and are activated by PDGF receptors. Tyr 740 and tyr 751 in PDGF beta-receptor, and tyr 731 and tyr 742 in PDGF alpha-receptor have been shown to be autophosphorylation sites and to bind PI3-kinase.

REACT_17059 (Reactome) After dimerization of the PDGF-A and PDGF-B chains in the ER of producing cells, the dimers are proteolytically cleaved in the trans-Golgi network during protein maturation and secretion. The dibasic-specific proprotein convertase, furin, or related convertases are involved in the conversion of proPDGF forms to active PDGF forms.
REACT_17063 (Reactome) Grb7 an adapter protein contains a single SH2 domain, a pleckstrin homology (PH) domain, and a proline-rich region. Similar to Grb2, Grb7 interacts with phosphorylated tyrosines in pYXNX motifs, including Tyr716 and Tyr775 of the PDGF beta-receptor.
SRC-1REACT_17048 (Reactome)
SRC-1mim-catalysisREACT_16991 (Reactome)
STAT family membersREACT_16982 (Reactome)
p-4Y-PLCG1ArrowREACT_111066 (Reactome)
p21 RAS:GDPREACT_16923 (Reactome)
p21 RAS:GTPArrowREACT_16923 (Reactome)
serine-type

endopeptidases involved in novel

PDGF processing		mim-catalysisREACT_16891 (Reactome)
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