PDGF pathway (WP2526)

PDGF belongs to the PDGF/VEGF (vascular endothelial growth factor) family, which is characterized by eight strictly conserved cysteine residues with similar spacing in between (Joukov et al., 1997; Heldin and Westermark, 1999). The A-, B-, C-, and D-chain genes of PDGF are localized to the chromosomes 7p22, 22q13, 4q31, and 11q22, respectively, and their expression is independently regulated. Two forms of the PDGF A-chain, containing 196 and 211 amino acid residues resulting from differential splicing of the transcript, are synthesized, dimerized, proteolytically processed in the Nterminus, and secreted from the cell as a ~30 kDa dimer. The PDGF B chain encoding 241 amino acid residues is dimerized, processed by additional proteolysis, and secreted as a 24 kDa dimer. The homodimers PDGF AA, BB, and the heterodimer AB contain three intrachain disulfide bonds made between the 1st. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2526 CPTAC Assay Portal]
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Authors

Amanzo, MaintBot, Mkutmon, Egonw, Khanspers, Zari, AlexanderPico, and Eweitz

Cited In

Organism

Homo sapiens

Communities

CPTAC

Annotations

Disease Ontology: cancer

Pathway Ontology: Jak-Stat signaling pathway platelet-derived growth factor signaling pathway

Participants

Label Type Compact Identifier
GRB2 Protein uniprot:P62993
STAT1 Protein uniprot:P42224
STAT3 Protein uniprot:P40763
NFKB1 GeneProduct kegg.genes:4790
AP-1(c-Jun) GeneProduct uniprot:P05412
RASA1(GAP) GeneProduct ensembl:ENSG00000145715
SH-PTP2(PTN11) GeneProduct uniprot:Q06124
SOS1 Protein uniprot:Q07889
RAF1 Protein uniprot:P04049
PDGFRB GeneProduct ensembl:ENSG00000113721
MAPK8(JNK1) GeneProduct uniprot:P45983
SHC1 Protein uniprot:P29353
MAPK3 GeneProduct ncbigene:5595
MAP2K4(JNKK1) GeneProduct ncbigene:6416
PLCG1 GeneProduct ensembl:ENSG00000124181
PDGFA GeneProduct ncbigene:5154
MAPK1 GeneProduct ncbigene:5594
MAP3K1(MEKK1) GeneProduct uniprot:Q13233
PDGFB GeneProduct ncbigene:5155
MP2K1(MEK 1) GeneProduct uniprot:Q02750
H-Ras-1(Ras) GeneProduct ncbigene:3265
PDGFA GeneProduct ncbigene:5154
NFKB1 GeneProduct ncbigene:4790
STAT1 Protein uniprot:P42224
STAT3 Protein uniprot:P40763
STAT3 Protein uniprot:P40763
STAT1 Protein uniprot:P42224
STAT3 Protein uniprot:P40763
STAT1 Protein uniprot:P42224
JAK1 Protein uniprot:P23458
Cyclic AMP(cAMP) Metabolite hmdb:HMDB0000058
DAG Metabolite lipidmaps:LMGL02010000
Prostaglandin I2(PGI2) Metabolite hmdb:HMDB0001335
IP3 Metabolite chebi:16595
COX2 Protein uniprot:P00403
PIP2[4,5] Metabolite lipidmaps:LMGP08010003
Ca2+ Metabolite chebi:29108
Phospholipid(containing arachidonic acid) Metabolite chebi:16247
PLA2G4A(cPLA2) GeneProduct ensembl:ENSG00000116711
Cell proliferation Pathway None
Cachannel Protein None
[Ca2+]i Metabolite chebi:29108
Arachidonic acid Metabolite hmdb:HMDB0001043
ELK1 GeneProduct uniprot:P19419
c-Fos GeneProduct uniprot:P01100
SRF GeneProduct uniprot:P11831
Na+/H+exchanger Protein None
H+ Metabolite chebi:15378
Na Metabolite chebi:29101
PI3K Protein uniprot:P27986
c-Src Protein uniprot:P12931
TIAM1 Protein uniprot:Q13009
Vav2 Protein uniprot:P52735
Rac1 Protein uniprot:P63000
RhoA Protein uniprot:P61586
Por1(ARF1P2) Protein uniprot:P53365
PAK1 Protein uniprot:Q13153
Vav1 Protein uniprot:P15498
CDC42 Protein uniprot:P60953
N-WASP Protein uniprot:O00401
FilopodiaFormation Pathway None
Actin,Stress Fibersand Adhesion Pathway wikipathways:WP306
LamellipodiaFormation Pathway None
Cell Migration Pathway None
IKK Protein uniprot:O15111
AktPathway Pathway None
IkB alpha GeneProduct uniprot:P25963
Degradation Pathway None

References

  1. Antoniades HN. PDGF: a multifunctional growth factor. Baillieres Clin Endocrinol Metab. 1991 Dec;5(4):595–613. PubMed Europe PMC Scholia
  2. Kawahara RS, Deng ZW, Deuel TF. PDGF and the small inducible gene (SIG) family: roles in the inflammatory response. Adv Exp Med Biol. 1991;305:79–87. PubMed Europe PMC Scholia
  3. Claesson-Welsh L, Heldin CH. Platelet-derived growth factor. Three isoforms that bind to two distinct cell surface receptors. Acta Oncol. 1989;28(3):331–4. PubMed Europe PMC Scholia
  4. Hannink M, Donoghue DJ. Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim Biophys Acta. 1989 Jul 28;989(1):1–10. PubMed Europe PMC Scholia
  5. Heldin CH, Westermark B. Platelet-derived growth factors: a family of isoforms that bind to two distinct receptors. Br Med Bull. 1989 Apr;45(2):453–64. PubMed Europe PMC Scholia
  6. Heldin CH, Hammacher A, Nistér M, Westermark B. Structural and functional aspects of platelet-derived growth factor. Br J Cancer. 1988 Jun;57(6):591–3. PubMed Europe PMC Scholia
  7. Andrae J, Gallini R, Betsholtz C. Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008 May 15;22(10):1276–312. PubMed Europe PMC Scholia
  8. Smith CL, Tallquist MD. PDGF function in diverse neural crest cell populations. Cell Adh Migr. 2010;4(4):561–6. PubMed Europe PMC Scholia
  9. Farooqi AA, Waseem S, Riaz AM, Dilawar BA, Mukhtar S, Minhaj S, et al. PDGF: the nuts and bolts of signalling toolbox. Tumour Biol. 2011 Dec;32(6):1057–70. PubMed Europe PMC Scholia
  10. Heldin C-H. Autocrine PDGF stimulation in malignancies. Ups J Med Sci. 2012 May;117(2):83–91. PubMed Europe PMC Scholia