Signaling by PDGF (Homo sapiens)

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1-32, 18, 192, 12, 131, 2, 222, 1732, 25, 262, 193, 63221, 2, 241, 2, 232, 2222, 10, 111, 2, 14, 151, 7-92, 20, 213, 6216extracellular regioncytosolendoplasmic reticulum lumenGolgi lumenATPC3G isoform 1NCKATPserine-type endopeptidases involved in novel PDGF processingPDGF:phospho-PDGF receptor dimer:STATPhosphatidylinositol-4,5-bisphosphateADPActive PDGF dimers (CC, DD)Novel PDGF precursor dimers (CC, DD)diacylglycerolsPhospho PDGF beta receptor: PDGF chain B homodimerPDGF:Phospho-PDGF receptor dimer:phospho-SrcPhospho-beta receptor homodimer:GAPGTP1D-myo-Inositol 1,4,5-trisphosphateATPADPPDGF alpha receptor: PDGF dimersp130CasActive PDGF dimers (AA, AB, BB)Phospholipase C gamma 1PDGF:Phospho-PDGF receptor dimer:Crk:p130Cas:C3GPDGF A and B chains with retention motifPDGF:Phospho-PDGF receptor dimer:CrkPhosphatidylinositol-4,5-bisphosphatePDGF:Phospho-PDGF receptor dimer:SHP2H2OADPExtracellular matrix ligandsNovel PDGF precursor dimers (CC, DD)PDGF precursor dimers (AA, BB, A/B, CC, DD)PDGF:Phospho-PDGF receptor dimer:SrcADPp21 RAS:GDPGRB2:SOS1RAF activationPDGF:Phospho-PDGF receptor dimer:PI3Kp21 RAS:GTPATPMAP kinase cascadeATPPDGF beta receptor:PDGF chain B homodimerPDGF:PDGF receptor dimerPDGF:Phospho-PDGF receptor dimer:Grb7furinPDGF A and B chains:ECM complexCleaved novel PDGF fragmentsPDGF alpha/beta:PDGF AB and BB dimersPDGF:Phospho-PDGFR receptor dimer:NckSHP2Crk isoformsPDGF:Phospho-PDGF receptor dimer:PLC-gammaGrb7Phospho PDGF alpha-beta dimer:PDGF AB or BB dimersPDGF:Phospho-PDGF receptor dimer:Grb2:Sos1PDGF receptor monomerCleaved classical PDGF peptidesPhosphatidylinositol-3,4,5-trisphosphateGDPPDGF precursor dimers (AA, BB, A/B, CC, DD)PI3KPDGF:Phospho-PDGF receptor dimerADPRas GTPase-activating protein 1Phospho PDGF alpha receptor:PDGF dimersClassical PDGF precursor dimers (AA, AB, BB)SRCSTAT family members54


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.

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Bibliography

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  1. Turjanski AG, Vaqué JP, Gutkind JS.; ''MAP kinases and the control of nuclear events.''; PubMed Europe PMC Scholia
  2. Yokote K, Margolis B, Heldin CH, Claesson-Welsh L.; ''Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors.''; PubMed Europe PMC Scholia
  3. Yokote K, Hellman U, Ekman S, Saito Y, Rönnstrand L, Saito Y, Heldin CH, Mori S.; ''Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins.''; PubMed Europe PMC Scholia
  4. Kashishian A, Kazlauskas A, Cooper JA.; ''Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo.''; PubMed Europe PMC Scholia
  5. Kashishian A, Cooper JA.; ''Phosphorylation sites at the C-terminus of the platelet-derived growth factor receptor bind phospholipase C gamma 1.''; PubMed Europe PMC Scholia
  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

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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
1D-myo-Inositol

1,4,5-trisphosphate

Metabolite16595 (ChEBI)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Active PDGF dimers

(AA, AB, BB)

ComplexREACT_17845 (Reactome)
Active PDGF dimers

(CC, DD)

ComplexREACT_17802 (Reactome)
C3G isoform 1 ProteinQ13905-1 (UniProt)
Classical PDGF

precursor dimers (AA, AB, BB)

ComplexREACT_17671 (Reactome)
Cleaved classical

PDGF peptides

ProteinREACT_17262 (Reactome)
Cleaved novel PDGF

fragments

ProteinREACT_18041 (Reactome)
Crk isoforms ProteinREACT_17492 (Reactome)
Extracellular matrix

ligands

ProteinREACT_17129 (Reactome)
GDP Metabolite17552 (ChEBI)
GRB2:

SOS1

ComplexREACT_4435 (Reactome)
GTP Metabolite15996 (ChEBI)
Grb7 ProteinQ14451 (UniProt)
H2O Metabolite15377 (ChEBI)
MAP kinase

cascade

PathwayREACT_634 (Reactome) 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.
NCK ProteinREACT_17190 (Reactome)
Novel PDGF

precursor dimers (CC, DD)

ComplexREACT_17079 (Reactome)
Novel PDGF

precursor dimers (CC, DD)

ComplexREACT_17162 (Reactome)
PDGF A and B chains

with retention motif

ProteinREACT_17714 (Reactome)
PDGF A and B chains:

ECM complex

ComplexREACT_17710 (Reactome)
PDGF alpha

receptor: PDGF dimers

ComplexREACT_17393 (Reactome)
PDGF alpha/beta:

PDGF AB and BB dimers

ComplexREACT_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

monomer

ProteinREACT_18211 (Reactome)
PDGF:PDGF receptor

dimer

ComplexREACT_18025 (Reactome)
PDGF:Phospho-

PDGFR receptor dimer:Nck

ComplexREACT_17490 (Reactome)
PDGF:Phospho-PDGF

receptor dimer

ComplexREACT_17756 (Reactome)
PDGF:Phospho-PDGF

receptor dimer: phospho-Src

ComplexREACT_17206 (Reactome)
PDGF:Phospho-PDGF

receptor dimer:Crk

ComplexREACT_17941 (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: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:STAT

ComplexREACT_17883 (Reactome)
PI3K ComplexREACT_4240 (Reactome)
Phosphatidylinositol-

3,4,5-trisphosphate

Metabolite16618 (ChEBI)
Phosphatidylinositol-

4,5-bisphosphate

Metabolite18348 (ChEBI)
Phospho PDGF

alpha-beta dimer: PDGF AB or BB dimers

ComplexREACT_17875 (Reactome)
Phospho PDGF alpha

receptor:PDGF dimers

ComplexREACT_17261 (Reactome)
Phospho PDGF beta

receptor: PDGF chain B homodimer

ComplexREACT_17403 (Reactome)
Phospho-beta

receptor homodimer:GAP

ComplexREACT_17783 (Reactome)
Phospholipase C

gamma 1

ProteinP19174 (UniProt)
RAF activation PathwayREACT_2077 (Reactome) Phosphorylated RAF is activated by Ras binding and stabilised in its active form by transient disassociation and reassociation of 14-3-3, as well as further phosphorylation.
Ras GTPase-

activating protein 1

ProteinP20936 (UniProt)
SHP2 ProteinQ06124 (UniProt)
SRC ProteinP12931-1 (UniProt)
STAT family

members

ProteinREACT_17706 (Reactome)
diacylglycerols Metabolite18035 (ChEBI)
furin ProteinP09958 (UniProt)
p130Cas ProteinP56945 (UniProt)
p21 RAS:GDP ComplexREACT_2657 (Reactome)
p21 RAS:GTP ComplexREACT_4782 (Reactome)
serine-type

endopeptidases involved in novel PDGF processing

UnknownREACT_17837 (Reactome)

Annotated Interactions

No annotated interactions

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