Signaling by PDGF (Homo sapiens)

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8, 27, 28277, 8, 273, 12281318, 22, 276, 16, 2719, 282710, 27272, 2724, 27, 291, 8, 14, 232, 17, 278, 15, 26, 274, 272819, 285, 9, 273274, 8, 278, 20, 27Collagen alpha-3PDGF B homodimer PDGF A homodimer PDGF A/B heterodimer PDGF B homodimer Active platelet-derived growth factor A chain isoforms PDGF A homodimer Active platelet-derived growth factor A chain isoforms Phospho-alpha receptor homodimer Processed PDGF-B PDGF alpha receptor PDGF dimers PDGF A/B heterodimer Phospho-alpha-Phospho-beta receptor heterodimer PDGFPhospho-PDGF receptor dimerCrk Active platelet-derived growth factor A chain isoforms Phospho-beta receptor homodimer PDGF A/B heterodimer PDGF A/B heterodimer Processed PDGF-B Collagen alpha-1Processed PDGF-B PDGF A/B heterodimer Active platelet-derived growth factor A chain isoforms p21 RASGDP endoplasmic reticulum lumenPI3K-regulatory subunit PDGF B homodimer Phospho-beta receptor homodimer PDGF A/B heterodimer Phospho-alpha-Phospho-beta receptor heterodimer Phospho-beta receptor homodimer Phospho-alpha receptor homodimer PDGF B homodimer Active platelet-derived growth factor A chain isoforms PDGFPDGF receptor dimer Phospho-alpha-Phospho-beta receptor heterodimer PDGF A homodimer Phospho PDGF alpha-beta dimerPDGF AB or BB dimers PDGFPhospho-PDGF receptor dimerCrkp130CasC3G PDGF AB or BB homodimers Phospho- PDGF receptor dimer PDGF A/B heterodimer Active platelet-derived growth factor A chain isoforms Phospho- PDGF receptor dimer PDGF A homodimer PDGFPhospho-PDGF receptor dimerPLC-gamma PDGF B homodimer PDGF A homodimer Phospho-beta receptor homodimer Processed PDGF-B Tropocollagen type VI Active platelet-derived growth factor A chain isoforms p21 RASGTP Phospho-alpha-Phospho-beta receptor heterodimer Phospho PDGF beta receptor PDGF chain B homodimer Phospho PDGF alpha receptorPDGF dimers Active PDGF dimers Phospho-beta receptor homodimer PDGF A/B heterodimer PDGFPhospho-PDGF receptor dimer PDGF A/B heterodimer cytosolPhospho-alpha receptor homodimer PDGF A/B heterodimer PDGFPhospho-PDGF receptor dimer Phospho-alpha receptor homodimer Extracellular matrix ligands PDGF A homodimer Active PDGF dimers Phospho-beta receptor homodimer Active PDGF dimers PDGF A/B heterodimer Processed PDGF-B PDGF B homodimer GRB2SOS1 PI3K-regulatory subunit Active PDGF dimers Active PDGF dimers CRK, CRKL Alpha receptor homodimer Active PDGF dimers Phospho-alpha-Phospho-beta receptor heterodimer Beta receptor homodimer Phospho-beta receptor homodimerGAP PDGFPhospho-PDGF receptor dimer Processed PDGF-B Processed PDGF-B PDGF A homodimer Processed PDGF-B Thrombospondin Collagen type IX Active PDGF dimers Phospho- PDGF receptor dimer Processed PDGF-B GRB2SOS1 PDGF A/B heterodimer Alpha-Beta receptor heterodimer PDGF AB or BB homodimers Beta receptor homodimer PDGF A homodimer Active PDGF dimers PDGF A homodimer Phospho-alpha-Phospho-beta receptor heterodimer PDGF A homodimer PDGFPhospho-PDGF receptor dimerSrc Phospho-alpha receptor homodimer Processed PDGF-B Phospho-beta receptor homodimer PI3K-catalytic subunit Phospho-beta receptor homodimer PI3K Phospho- PDGF receptor dimer PDGFPhospho-PDGF receptor dimerSHP2 Collagens Phospho-beta receptor homodimer PDGFPhospho-PDGF receptor dimer PDGF B homodimer PDGF B homodimer PDGFphospho-PDGF receptor dimerSTAT Processed PDGF-B Active PDGF dimers Active platelet-derived growth factor A chain isoforms Phospho-beta receptor homodimer PDGF B homodimer NCK Phospho- PDGF receptor dimer Phospho-alpha-Phospho-beta receptor heterodimer PDGF A/B heterodimer Phospho-alpha receptor homodimer Phospho- PDGF receptor dimer Processed PDGF-B Phospho-alpha-Phospho-beta receptor heterodimer Phospho-alpha receptor homodimer Phospho- PDGF receptor dimer PDGFPhospho-PDGF receptor dimerphospho-Src PDGF A homodimer Active platelet-derived growth factor A chain isoforms Processed PDGF-B Golgi lumenPDGF alpha/betaPDGF AB and BB dimers PDGFPhospho-PDGFR receptor dimerNck Active PDGF dimers PDGFPhospho-PDGF receptor dimer Active platelet-derived growth factor A chain isoforms Phospho-alpha-Phospho-beta receptor heterodimer Active platelet-derived growth factor A chain isoforms Alpha-Beta receptor heterodimer Phospho-alpha-Phospho-beta receptor heterodimer Phospho PDGF beta receptor PDGF chain B homodimer Active PDGF dimers PDGF A homodimer PDGF B homodimer Phospho-alpha receptor homodimer Phospho-alpha receptor homodimer PDGF B homodimer Active PDGF dimers Processed PDGF-B PDGF B homodimer Phospho-alpha-Phospho-beta receptor heterodimer Phospho-alpha receptor homodimer Phospho-alpha-Phospho-beta receptor heterodimer PDGF B homodimer Type IV collagen Processed PDGF-B PDGF B homodimer PDGF A and B chains with retention motif Active platelet-derived growth factor A chain isoforms CRK, CRKL Phospho- PDGF receptor dimer Active platelet-derived growth factor A chain isoforms Phospho-beta receptor homodimer PDGF A/B heterodimer PDGFPhospho-PDGF receptor dimerGrb2Sos1 Processed PDGF-B Phospho-beta receptor homodimer Phospho-alpha receptor homodimer STAT family members PDGF B homodimer PDGFPhospho-PDGF receptor dimer Active platelet-derived growth factor A chain isoforms p21 RAS Phospho-beta receptor homodimer Phospho-alpha receptor homodimer Active PDGF dimers Alpha receptor homodimer Collagen alpha-1Phospho- PDGF receptor dimer Collagen alpha-2PDGF A homodimer PDGF A/B heterodimer Processed PDGF-B PDGFPhospho-PDGF receptor dimer Phospho- PDGF receptor dimer Phospho-alpha-Phospho-beta receptor heterodimer Processed PDGF-B PI3K PDGFp-PDGFR dimerp-PLCgamma Phospho-beta receptor homodimer Active platelet-derived growth factor A chain isoforms PDGF beta receptorPDGF chain B homodimer PDGF A/B heterodimer PDGFPhospho-PDGF receptor dimerPI3K PDGF A homodimer Heparan sulphate PDGF A/B heterodimer Active PDGF dimers Phospho-alpha-Phospho-beta receptor heterodimer PI3K-catalytic subunit Phospho-beta receptor homodimer Processed PDGF-B Active PDGF dimers PDGFPhospho-PDGF receptor dimerGrb7 p21 RAS PDGF B homodimer PDGF A/B heterodimer PDGF B homodimer PDGF B homodimer PDGF A and B chainsECM complex Phospho- PDGF receptor dimer Phospho- PDGF receptor dimer Active PDGF dimers PDGF A homodimer PDGF A homodimer PDGFPhospho-PDGF receptor dimerCrk Phospho-alpha receptor homodimer PDGF B homodimer Processed PDGF-B PDGF receptor dimer Phospho- PDGF receptor dimer Active platelet-derived growth factor A chain isoforms PDGF B homodimer PDGF B homodimer Processed PDGF-B Phospho-alpha receptor homodimer COL9A2 PDGFA-2 PIK3CA p-11Y-PDGFRA p-11Y-PDGFRA RAPGEF1 COL4A4PDGFphospho-PDGF receptor dimerSTATPDGFA-1 PDGFB p-12Y-PDGFRB PDGFA-1 PDGFA-2 p-12Y-PDGFRB p-12Y-PDGFRB p-11Y-PDGFRA HRASPDGFB p-12Y-PDGFRB p-12Y-PDGFRB KRASPDGFBCOL6A2 PDGFBPDGF A and B chainsECM complexPDGFBGalHyl-COL6A2 PDGFB PDGFBPDGFA-2 PDGFA-1 3x4Hyp-3Hyp-5Hyl-COL6A1 PDGFBPDGFPhospho-PDGF receptor dimerSrcPIK3R1 NCKPLCG1PIK3CB PIK3CA PDGFBPDGFA-1 STAT1 3x4Hyp-3Hyp-GalHyl-COL6A1 PIPDGFB PDGFA-2 ATPPDGFRB ATPp-11Y-PDGFRA PDGFB PI3KCRKPDGFBPDGF alpha receptor PDGF dimersPDGFBPDGFA-2 COL4A3PDGFA-1 p-12Y-PDGFRB STAT5B PDGFB BCAR1p-11Y-PDGFRA PDGFBp-Y419-SRC-1 3x4Hyp-COL6A2 5Hyl-COL6A1 p-4Y-PLCG1 GRB2-1 p-11Y-PDGFRA p21 RASGDPPDGFA-2 PDGFA-1 GlcGalHyl-COL6A1 PDGFRB PDGFp-PDGFR dimerp-PLCgammaPDGFA-1 p-12Y-PDGFRB THBS1 p-11Y-PDGFRA 3x4Hyp-3Hyp-5Hyl-COL6A2 p21 RASGTPPIK3R2 BCAR1 Novel PDGF precursor dimers PDGFBPDGF beta receptorPDGF chain B homodimer3x4Hyp-3Hyp-GlcGalHyl-COL6A2 GRB2SOS1SPP1PDGFBPDGFPhospho-PDGFR receptor dimerNckPDGFA-2 p-12Y-PDGFRB PDGFBPDGFBCRKATPSTAT3 p-4Y-PLCG1p-11Y-PDGFRA ADPPDGFA-1 PDGFA-2 SRC-1 RAPGEF1p-11Y-PDGFRA 3x4Hyp-3Hyp-COL6A2 3x4Hyp-GlcGalHyl-COL6A1 p-11Y-PDGFRA PDGFBCRKL GlcGalHyl-COL6A2 NRAS STAT6 PDGFBRASA1 PDGFB GDPNCK1 ADPPTPN11PDGFA-1 CRKL PDGFPhospho-PDGF receptor dimerPI3KPDGF A and B chains with retention motifCleaved classical PDGF peptidesGTP PDGFRA PDGFA-1 PDGFBPDGF precursor dimers PDGFB THBS4 PDGFA-1 PDGFA-1 PDGFA-1 PDGFA-1 COL6A1 Heparan sulfate N-acetyl-alpha-D-glucosaminide 3x4Hyp-GalHyl-COL6A2 PDGFA-2 3x4Hyp-3Hyp-GlcGalHyl-COL6A1 PIK3R1 Active PDGF dimers PDGFBGRB2-1 3x4Hyp-COL6A1 DAG and IP3 signalingp-11Y-PDGFRA PIPDGFB PDGFBp-12Y-PDGFRB PLCG1Phospho PDGF beta receptor PDGF chain B homodimerp-12Y-PDGFRB RASA1PDGFA-1 p-12Y-PDGFRB PDGFPDGF receptor dimer5Hyl-COL6A2 KRASPDGFA-2 PDGF receptor monomerp-11Y-PDGFRA GTPSTAT family membersPDGFB p-11Y-PDGFRA PDGF precursor dimers PDGFB serine-type endopeptidases involved in novel PDGF processingp-11Y-PDGFRA GRB7 3x4Hyp-5Hyl-COL6A2 RAF/MAP kinase cascadePDGFPhospho-PDGF receptor dimerSHP2Phospho-beta receptor homodimerGAPCleaved novel PDGF fragmentsNRAS PDGFPhospho-PDGF receptor dimerGrb7PDGFB Phospho PDGF alpha receptorPDGF dimersTHBS3 p-12Y-PDGFRB 3x4Hyp-3Hyp-COL6A1 PDGFA-2 SOS1 SOS1 SRC-1PDGFB COL4A5PDGFPhospho-PDGF receptor dimerGrb2Sos1p-12Y-PDGFRB ADPPTPN11 PDGFA-2 COL9A3 Phospho PDGF alpha-beta dimerPDGF AB or BB dimersPDGFA-2 PDGFRB PDGFBPDGFPhospho-PDGF receptor dimerCrkPDGFB PDGFRA Active PDGF dimers PDGFPhospho-PDGF receptor dimerPLC-gammap-12Y-PDGFRB THBS2 PDGFA-1 HRASADPp-12Y-PDGFRB STAT5A 3x4Hyp-GlcGalHyl-COL6A2 3x4Hyp-GalHyl-COL6A1 3x4Hyp-5Hyl-COL6A1 PDGFA-1 ADPGRB7ATPNCK2 FURINClassical PDGF precursor dimers PIP3 activates AKT signalingp-12Y-PDGFRB COL9A1 PDGFB PDGFA-2 p-11Y-PDGFRA COL4A1PDGFBHeparan sulfate alpha-D-glucosaminide PDGFPhospho-PDGF receptor dimerCrkp130CasC3GPDGFA-2 PDGFA-2 PIK3CB PDGFBATPGDP Extracellular matrix ligandsPDGFB PIK3R2 PDGFBPDGFB PDGFA-2 3x4Hyp-3Hyp-GalHyl-COL6A2 PDGFB PDGFA-2 Novel PDGF precursor dimers CRK, CRKLPDGF alpha/betaPDGF AB and BB dimersPDGFB PDGFPhospho-PDGF receptor dimerCOL4A2PDGFRA GalHyl-COL6A1 PDGFB PDGFPhospho-PDGF receptor dimerphospho-SrcPDGFB 112521, 30


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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Bibliography

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History

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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 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GalHyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GalHyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GlcGalHyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-GlcGalHyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-5Hyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-5Hyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-GalHyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-GalHyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-GlcGalHyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-GlcGalHyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
5Hyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
5Hyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Active PDGF dimers ComplexREACT_17802 (Reactome)
Active PDGF dimers ComplexREACT_17845 (Reactome)
BCAR1 ProteinP56945 (Uniprot-TrEMBL)
BCAR1ProteinP56945 (Uniprot-TrEMBL)
COL4A1ProteinP02462 (Uniprot-TrEMBL)
COL4A2ProteinP08572 (Uniprot-TrEMBL)
COL4A3ProteinQ01955 (Uniprot-TrEMBL)
COL4A4ProteinP53420 (Uniprot-TrEMBL)
COL4A5ProteinP29400 (Uniprot-TrEMBL)
COL6A1 ProteinP12109 (Uniprot-TrEMBL)
COL6A2 ProteinP12110 (Uniprot-TrEMBL)
COL9A1 ProteinP20849 (Uniprot-TrEMBL)
COL9A2 ProteinQ14055 (Uniprot-TrEMBL)
COL9A3 ProteinQ14050 (Uniprot-TrEMBL)
CRK, CRKLProteinREACT_17492 (Reactome)
CRKL ProteinP46109 (Uniprot-TrEMBL)
CRKProteinP46108 (Uniprot-TrEMBL)
Classical PDGF precursor dimers 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 MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRB2 SOS1ComplexREACT_4435 (Reactome)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GRB7 ProteinQ14451 (Uniprot-TrEMBL)
GRB7ProteinQ14451 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
GalHyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
GalHyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
GlcGalHyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
GlcGalHyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
HRASProteinP01112 (Uniprot-TrEMBL)
Heparan sulfate N-acetyl-alpha-D-glucosaminide MetaboliteCHEBI:17421 (ChEBI)
Heparan sulfate alpha-D-glucosaminide MetaboliteCHEBI:18137 (ChEBI)
KRASProteinP01116 (Uniprot-TrEMBL)
NCK1 ProteinP16333 (Uniprot-TrEMBL)
NCK2 ProteinO43639 (Uniprot-TrEMBL)
NCKProteinREACT_17190 (Reactome)
NRAS ProteinP01111 (Uniprot-TrEMBL)
Novel PDGF precursor dimers ComplexREACT_17079 (Reactome)
Novel PDGF precursor dimers ComplexREACT_17162 (Reactome)
PDGF PDGF receptor dimerComplexREACT_18025 (Reactome)
PDGF

Phospho-PDGF receptor dimer Crk p130Cas

C3G		ComplexREACT_17351 (Reactome)
PDGF

Phospho-PDGF receptor dimer

Crk		ComplexREACT_17941 (Reactome)
PDGF

Phospho-PDGF receptor dimer Grb2

Sos1		ComplexREACT_18248 (Reactome)
PDGF

Phospho-PDGF receptor dimer

Grb7		ComplexREACT_17607 (Reactome)
PDGF

Phospho-PDGF receptor dimer

PI3K		ComplexREACT_17825 (Reactome)
PDGF

Phospho-PDGF receptor dimer

PLC-gamma		ComplexREACT_17327 (Reactome)
PDGF

Phospho-PDGF receptor dimer

SHP2		ComplexREACT_17654 (Reactome)
PDGF

Phospho-PDGF receptor dimer

Src		ComplexREACT_18132 (Reactome)
PDGF

Phospho-PDGF receptor dimer

phospho-Src		ComplexREACT_17206 (Reactome)
PDGF Phospho-PDGF receptor dimerComplexREACT_17756 (Reactome)
PDGF

Phospho-PDGFR receptor dimer

Nck		ComplexREACT_17490 (Reactome)
PDGF

p-PDGFR dimer

p-PLCgamma		ComplexREACT_111673 (Reactome)
PDGF

phospho-PDGF receptor dimer

STAT		ComplexREACT_17883 (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 homodimerComplexREACT_17457 (Reactome)
PDGF precursor dimers ComplexREACT_17541 (Reactome)
PDGF precursor dimers ComplexREACT_17912 (Reactome)
PDGF receptor monomerProteinREACT_18211 (Reactome)
PDGFA-1 ProteinP04085-1 (Uniprot-TrEMBL)
PDGFA-2 ProteinP04085-2 (Uniprot-TrEMBL)
PDGFB ProteinP01127 (Uniprot-TrEMBL)
PDGFBProteinP01127 (Uniprot-TrEMBL)
PDGFRA ProteinP16234 (Uniprot-TrEMBL)
PDGFRB ProteinP09619 (Uniprot-TrEMBL)
PI3KComplexREACT_4240 (Reactome)
PIMetaboliteCHEBI:16618 (ChEBI)
PIMetaboliteCHEBI:18348 (ChEBI)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PIK3CB ProteinP42338 (Uniprot-TrEMBL)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIK3R2 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.
PLCG1ProteinP19174 (Uniprot-TrEMBL)
PTPN11 ProteinQ06124 (Uniprot-TrEMBL)
PTPN11ProteinQ06124 (Uniprot-TrEMBL)
Phospho PDGF alpha receptor PDGF dimersComplexREACT_17261 (Reactome)
Phospho PDGF alpha-beta dimer PDGF AB or BB dimersComplexREACT_17875 (Reactome)
Phospho PDGF beta receptor PDGF chain B homodimerComplexREACT_17403 (Reactome)
Phospho-beta receptor homodimer GAPComplexREACT_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 ProteinQ13905 (Uniprot-TrEMBL)
RAPGEF1ProteinQ13905 (Uniprot-TrEMBL)
RASA1 ProteinP20936 (Uniprot-TrEMBL)
RASA1ProteinP20936 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
SPP1ProteinP10451 (Uniprot-TrEMBL)
SRC-1 ProteinP12931-1 (Uniprot-TrEMBL)
SRC-1ProteinP12931-1 (Uniprot-TrEMBL)
STAT family membersProteinREACT_17706 (Reactome)
STAT1 ProteinP42224 (Uniprot-TrEMBL)
STAT3 ProteinP40763 (Uniprot-TrEMBL)
STAT5A ProteinP42229 (Uniprot-TrEMBL)
STAT5B ProteinP51692 (Uniprot-TrEMBL)
STAT6 ProteinP42226 (Uniprot-TrEMBL)
THBS1 ProteinP07996 (Uniprot-TrEMBL)
THBS2 ProteinP35442 (Uniprot-TrEMBL)
THBS3 ProteinP49746 (Uniprot-TrEMBL)
THBS4 ProteinP35443 (Uniprot-TrEMBL)
p-11Y-PDGFRA ProteinP16234 (Uniprot-TrEMBL)
p-12Y-PDGFRB ProteinP09619 (Uniprot-TrEMBL)
p-4Y-PLCG1 ProteinP19174 (Uniprot-TrEMBL)
p-4Y-PLCG1ProteinP19174 (Uniprot-TrEMBL)
p-Y419-SRC-1 ProteinP12931-1 (Uniprot-TrEMBL)
p21 RAS GDPComplexREACT_2657 (Reactome)
p21 RAS GTPComplexREACT_4782 (Reactome)
serine-type endopeptidases involved in novel PDGF processingREACT_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 ArrowREACT_16891 (Reactome)
Active PDGF dimers ArrowREACT_17059 (Reactome)
Active PDGF dimers REACT_16905 (Reactome)
BCAR1REACT_16951 (Reactome)
CRK, CRKLREACT_16940 (Reactome)
Cleaved classical PDGF peptidesArrowREACT_17059 (Reactome)
Cleaved novel PDGF fragmentsArrowREACT_16891 (Reactome)
Extracellular matrix ligandsREACT_16880 (Reactome)
FURINREACT_17059 (Reactome)
GDPArrowREACT_16923 (Reactome)
GRB2 SOS1REACT_16901 (Reactome)
GRB7REACT_17063 (Reactome)
GTPREACT_16923 (Reactome)
NCKREACT_16997 (Reactome)
PDGF

Phospho-PDGF receptor dimer

Crk		REACT_16951 (Reactome)
PDGF

Phospho-PDGF receptor dimer Grb2

Sos1		REACT_16923 (Reactome)
PDGF

Phospho-PDGF receptor dimer

PI3K		REACT_16877 (Reactome)
PDGF

Phospho-PDGF receptor dimer

PLC-gamma		REACT_111134 (Reactome)
PDGF

Phospho-PDGF receptor dimer

Src		REACT_16991 (Reactome)
PDGF

Phospho-PDGF receptor dimer

phospho-Src		ArrowREACT_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 A and B chains with retention motifREACT_16880 (Reactome)
PDGF alpha receptor PDGF dimersREACT_16993 (Reactome)
PDGF alpha/beta PDGF AB and BB dimersREACT_17034 (Reactome)
PDGF beta receptor PDGF chain B homodimerREACT_16926 (Reactome)
PDGF receptor monomerREACT_16905 (Reactome)
PI3KREACT_17052 (Reactome)
PIArrowREACT_16877 (Reactome)
PIREACT_16877 (Reactome)
PLCG1REACT_16998 (Reactome)
PTPN11REACT_16960 (Reactome)
Phospho PDGF alpha receptor PDGF dimersArrowREACT_16993 (Reactome)
Phospho PDGF alpha-beta dimer PDGF AB or BB dimersArrowREACT_17034 (Reactome)
Phospho PDGF beta receptor PDGF chain B homodimerArrowREACT_16926 (Reactome)
Phospho PDGF beta receptor PDGF chain B homodimerREACT_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_16991 (Reactome)
SRC-1REACT_17048 (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 processingREACT_16891 (Reactome)
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