The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Pdgfa  -  platelet derived growth factor, alpha

Mus musculus

Synonyms: PDGF subunit A, PDGF-1, Platelet-derived growth factor A chain, Platelet-derived growth factor alpha polypeptide, Platelet-derived growth factor subunit A
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Pdgfa

  • Pdgfc(-/-) Pdgfa(-/-) embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects [1].
  • Dominant-negative mutations of PDGF and other growth factors which, like PDGF, function as dimers may prove useful for creating animals models of growth factor deficiency disease states and for revealing the function of growth factors during early embryonic development [2].
  • Because of its expression pattern and its potent effects on mesenchymal cells, platelet-derived growth factor (PDGF) has been implicated as an important factor in epithelial-mesenchymal cell interactions during normal lung development and in the pathogenesis of fibrotic lung disease [3].
  • These were used, together with a mouse PDGF receptor beta subunit cDNA clone, to monitor gene expression in early postimplantation mouse embryos and in F9 embryonal carcinoma cells [4].
  • In this study, the expression of interleukin (IL)-1 alpha and beta, platelet-derived growth factor (PDGF) A and B, and insulin-like growth factor (IGF) I in BAL cells, which may be involved in fibroblast proliferation, was investigated in murine bleomycin (BLM)-induced pulmonary fibrosis [5].

High impact information on Pdgfa

  • Mutations in these genes lead to a high frequency of phenotypes that affect the same cell types and processes as those controlled by the PDGF pathway [6].
  • PDGF signaling specificity is mediated through multiple immediate early genes [6].
  • Identification and validation of PDGF transcriptional targets by microarray-coupled gene-trap mutagenesis [7].
  • However, targetted inactivation of the Pdgfb gene or the Pdgf receptor beta (Pdgfrb) gene, by homologous recombination, does not prevent the development of apparently normal large arteries and connective tissue [8].
  • The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase [9].

Chemical compound and disease context of Pdgfa


Biological context of Pdgfa

  • Based on the established role of the platelet-derived growth factor (PDGF) family of ligands and receptors in migration, proliferation, and differentiation of cells in various organ systems, we have investigated the role of PDGF in testis organogenesis [15].
  • Several lines of evidence now exist to suggest an interaction between the platelet-derived growth factor (PDGF) growth-stimulatory signal transduction pathway and the beta interferon (IFN-beta) growth-inhibitory signal transduction pathway [16].
  • It appears that PDGF modulates a program of gene expression with the accumulation of some transcripts, typified by MEP, being dependent upon the translation of others [17].
  • Moreover, compared to wild-type cells, cellular proliferation stimulated by serum or platelet-derived growth factor (PDGF) was enhanced and accelerated in STAT1(-/-) HSCs, which was partially mediated via elevated PDGF receptor beta expression on such cells [18].
  • Down-regulation of PKC by prolonged treatment with 4 beta-phorbol 12-myristate 13-acetate also abolished EGF- and PDGF-stimulated phosphatidylbutanol formation [19].

Anatomical context of Pdgfa

  • Platelet-derived growth factor (PDGF) stimulates density-arrested BALB/c-3T3 cells to synthesize MEP, a lysosomal protein [17].
  • To investigate the significance of these observations, we have examined the role of PDGF signaling in the developing somite [20].
  • Platelet-derived growth factor (PDGF) B and A homodimers transform murine fibroblasts depending on the genetic background of the cell [21].
  • We now have established conditions in which subconfluent, logarithmically growing NIH 3T3 cells are efficiently transformed by exogenous PDGF B but not PDGF A [21].
  • The Cdc42(-/-) cells were defective in filopodia formation stimulated by bradykinin and in dorsal membrane ruffling stimulated by PDGF, whereas the Cdc42GAP(-/-) cells displayed spontaneous filopodia [22].

Associations of Pdgfa with chemical compounds

  • The block to signaling was not due to a defect in inositol phosphate metabolism, as PDGF treatment induced normal calcium mobilization and phosphotidylinositol-3-kinase activation in these cells [16].
  • Autophosphorylation of the platelet-derived growth factor (PDGF) receptor on tyrosine, which is dependent upon and occurs immediately after ligand binding, has been linked to the activation of second messenger pathways thought to be necessary for the induction of gene expression, DNA synthesis, and mitogenesis [23].
  • Platelet-derived growth factor (PDGF) receptor-alpha activates c-Jun NH2-terminal kinase-1 and antagonizes PDGF receptor-beta -induced phenotypic transformation [24].
  • Insulin potentiated the effects of IGF-1, EGF, and PDGF on DNA synthesis in cells expressing the wild type insulin receptor, but this potentiation was inhibited in the presence of the FTase inhibitor, alpha-hydroxyfarnesylphosphonic acid [25].
  • The effects of PDGF, EGF, and bFGF were completely abolished by pretreatment with actinomycin D, an inhibitor of RNA synthesis, suggesting a transcriptional mechanism [26].

Physical interactions of Pdgfa


Enzymatic interactions of Pdgfa

  • The EGF receptor is phosphorylated at tyrosine residues although we have not yet established if this represents direct phosphorylation by the PDGF receptor kinase or is mediated by activation of other cell membrane-associated tyrosine kinases [31].

Regulatory relationships of Pdgfa

  • PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor [32].
  • PDGF-A chain homodimer PDGF AA activates alpha-PDGFR only, and its role for cell migration is still debatable [33].
  • In addition, Src family kinases activate STAT signaling and are required for PDGF-induced mitogenesis in normal cells [34].
  • In normal NIH 3T3 cells, disruption of Stat3 signaling with dominant-negative Stat3beta protein inhibits PDGF-induced mitogenesis in a manner that is reversed by ectopic c-Myc expression [34].
  • The recruitment of the polyamine-depleted, serum-deprived cells into the cell division cycle does not require PDGF and can be induced by addition of EGF and insulin plus putrescine [35].

Other interactions of Pdgfa


Analytical, diagnostic and therapeutic context of Pdgfa


  1. A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling. Ding, H., Wu, X., Boström, H., Kim, I., Wong, N., Tsoi, B., O'Rourke, M., Koh, G.Y., Soriano, P., Betsholtz, C., Hart, T.C., Marazita, M.L., Field, L.L., Tam, P.P., Nagy, A. Nat. Genet. (2004) [Pubmed]
  2. Dominant-negative mutants of a platelet-derived growth factor gene. Mercola, M., Deininger, P.L., Shamah, S.M., Porter, J., Wang, C.Y., Stiles, C.D. Genes Dev. (1990) [Pubmed]
  3. Emphysematous lesions, inflammation, and fibrosis in the lungs of transgenic mice overexpressing platelet-derived growth factor. Hoyle, G.W., Li, J., Finkelstein, J.B., Eisenberg, T., Liu, J.Y., Lasky, J.A., Athas, G., Morris, G.F., Brody, A.R. Am. J. Pathol. (1999) [Pubmed]
  4. Selective expression of PDGF A and its receptor during early mouse embryogenesis. Mercola, M., Wang, C.Y., Kelly, J., Brownlee, C., Jackson-Grusby, L., Stiles, C., Bowen-Pope, D. Dev. Biol. (1990) [Pubmed]
  5. Increased expression of platelet-derived growth factor A and insulin-like growth factor-I in BAL cells during the development of bleomycin-induced pulmonary fibrosis in mice. Maeda, A., Hiyama, K., Yamakido, H., Ishioka, S., Yamakido, M. Chest (1996) [Pubmed]
  6. PDGF signaling specificity is mediated through multiple immediate early genes. Schmahl, J., Raymond, C.S., Soriano, P. Nat. Genet. (2007) [Pubmed]
  7. Identification and validation of PDGF transcriptional targets by microarray-coupled gene-trap mutagenesis. Chen, W.V., Delrow, J., Corrin, P.D., Frazier, J.P., Soriano, P. Nat. Genet. (2004) [Pubmed]
  8. Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages. Crosby, J.R., Seifert, R.A., Soriano, P., Bowen-Pope, D.F. Nat. Genet. (1998) [Pubmed]
  9. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Franke, T.F., Yang, S.I., Chan, T.O., Datta, K., Kazlauskas, A., Morrison, D.K., Kaplan, D.R., Tsichlis, P.N. Cell (1995) [Pubmed]
  10. The antiangiogenic agents SU5416 and SU6668 increase the antitumor effects of fractionated irradiation. Ning, S., Laird, D., Cherrington, J.M., Knox, S.J. Radiat. Res. (2002) [Pubmed]
  11. Renal platelet-derived growth factor gene expression in NZB/W F1 mice with lupus and ddY mice with IgA nephropathy. Nakamura, T., Ebihara, I., Nagaoka, I., Tomino, Y., Koide, H. Clin. Immunol. Immunopathol. (1992) [Pubmed]
  12. Characterization of biologically active, platelet-derived growth factor-like molecules produced by murine erythroid cells in vitro and in vivo. Sytkowski, A.J., O'Hara, C., Vanasse, G., Armstrong, M.J., Kreczko, S., Dainiak, N. J. Clin. Invest. (1990) [Pubmed]
  13. Compartmentalization of autocrine signal transduction pathways in Sis-transformed NIH 3T3 cells. Valgeirsdóttir, S., Eriksson, A., Nistér, M., Heldin, C.H., Westermark, B., Claesson-Welsh, L. J. Biol. Chem. (1995) [Pubmed]
  14. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. Buchdunger, E., Cioffi, C.L., Law, N., Stover, D., Ohno-Jones, S., Druker, B.J., Lydon, N.B. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  15. Pdgfr-alpha mediates testis cord organization and fetal Leydig cell development in the XY gonad. Brennan, J., Tilmann, C., Capel, B. Genes Dev. (2003) [Pubmed]
  16. BALB/c-3T3 fibroblasts resistant to growth inhibition by beta interferon exhibit aberrant platelet-derived growth factor, epidermal growth factor, and fibroblast growth factor signal transduction. Mundschau, L.J., Faller, D.V. Mol. Cell. Biol. (1991) [Pubmed]
  17. Regulation of the transcript for a lysosomal protein: evidence for a gene program modified by platelet-derived growth factor. Frick, K.K., Doherty, P.J., Gottesman, M.M., Scher, C.D. Mol. Cell. Biol. (1985) [Pubmed]
  18. STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity. Jeong, W.I., Park, O., Radaeva, S., Gao, B. Hepatology (2006) [Pubmed]
  19. Stimulation of phospholipase D by epidermal growth factor requires protein kinase C activation in Swiss 3T3 cells. Yeo, E.J., Exton, J.H. J. Biol. Chem. (1995) [Pubmed]
  20. Early myotome specification regulates PDGFA expression and axial skeleton development. Tallquist, M.D., Weismann, K.E., Hellström, M., Soriano, P. Development (2000) [Pubmed]
  21. Platelet-derived growth factor (PDGF) B and A homodimers transform murine fibroblasts depending on the genetic background of the cell. Kim, H.R., Upadhyay, S., Korsmeyer, S., Deuel, T.F. J. Biol. Chem. (1994) [Pubmed]
  22. Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic Fibroblasts. Yang, L., Wang, L., Zheng, Y. Mol. Biol. Cell (2006) [Pubmed]
  23. Platelet-derived growth factor (PDGF) induction of egr-1 is independent of PDGF receptor autophosphorylation on tyrosine. Mundschau, L.J., Forman, L.W., Weng, H., Faller, D.V. J. Biol. Chem. (1994) [Pubmed]
  24. Platelet-derived growth factor (PDGF) receptor-alpha activates c-Jun NH2-terminal kinase-1 and antagonizes PDGF receptor-beta -induced phenotypic transformation. Yu, J., Deuel, T.F., Kim, H.R. J. Biol. Chem. (2000) [Pubmed]
  25. Effect of insulin on farnesyltransferase. Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor. Goalstone, M.L., Leitner, J.W., Wall, K., Dolgonos, L., Rother, K.I., Accili, D., Draznin, B. J. Biol. Chem. (1998) [Pubmed]
  26. Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells. Okazaki, R., Ikeda, K., Sakamoto, A., Nakano, T., Morimoto, K., Kikuchi, T., Urakawa, K., Ogata, E., Matsumoto, T. J. Bone Miner. Res. (1992) [Pubmed]
  27. Molecular mechanism of basic calcium phosphate crystal-induced mitogenesis. Role of protein kinase C. Mitchell, P.G., Pledger, W.J., Cheung, H.S. J. Biol. Chem. (1989) [Pubmed]
  28. Early growth-responsive-1-dependent manganese superoxide dismutase gene transcription mediated by platelet-derived growth factor. Maehara, K., Oh-Hashi, K., Isobe, K.I. FASEB J. (2001) [Pubmed]
  29. Epidermal growth factor stimulates formation of inositol phosphates in BALB/c/3T3 cells pretreated with cholera toxin and isobutylmethylxanthine. Olashaw, N.E., Pledger, W.J. J. Biol. Chem. (1988) [Pubmed]
  30. Differential regulation of expression of two platelet-derived growth factor receptor subunits by transforming growth factor-beta. Gronwald, R.G., Seifert, R.A., Bowen-Pope, D.F. J. Biol. Chem. (1989) [Pubmed]
  31. Reconstitution of the high affinity epidermal growth factor receptor on cell-free membranes after transmodulation by platelet-derived growth factor. Walker, F., Burgess, A.W. J. Biol. Chem. (1991) [Pubmed]
  32. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Li, X., Pontén, A., Aase, K., Karlsson, L., Abramsson, A., Uutela, M., Bäckström, G., Hellström, M., Boström, H., Li, H., Soriano, P., Betsholtz, C., Heldin, C.H., Alitalo, K., Ostman, A., Eriksson, U. Nat. Cell Biol. (2000) [Pubmed]
  33. Both platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta promote murine fibroblast cell migration. Yu, J., Moon, A., Kim, H.R. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  34. Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Bowman, T., Broome, M.A., Sinibaldi, D., Wharton, W., Pledger, W.J., Sedivy, J.M., Irby, R., Yeatman, T., Courtneidge, S.A., Jove, R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  35. Resumption of cell cycle in BALB/c-3T3 fibroblasts arrested by polyamine depletion: relation with "competence" gene expression. Charollais, R.H., Mester, J. J. Cell. Physiol. (1988) [Pubmed]
  36. Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor AB (PDGF AB) promote adult SVZ-derived oligodendrogenesis in vivo. Lachapelle, F., Avellana-Adalid, V., Nait-Oumesmar, B., Baron-Van Evercooren, A. Mol. Cell. Neurosci. (2002) [Pubmed]
  37. Expression of platelet-derived growth factor (PDGF) in the epididymis and analysis of the epididymal development in PDGF-A, PDGF-B, and PDGF receptor beta deficient mice. Basciani, S., Mariani, S., Arizzi, M., Brama, M., Ricci, A., Betsholtz, C., Bondjers, C., Ricci, G., Catizone, A., Galdieri, M., Spera, G., Gnessi, L. Biol. Reprod. (2004) [Pubmed]
  38. Transforming growth factor beta 1-induced delay of cell cycle progression and its association with growth-related gene expression in mouse fibroblasts. Kim, T.A., Cutry, A.F., Kinniburgh, A.J., Wenner, C.E. Cancer Lett. (1993) [Pubmed]
  39. Aberrant expression of PDGF ligands and receptors in the tumor prone ovary of follitropin receptor knockout (FORKO) mouse. Chen, X., Aravindakshan, J., Yang, Y., Tiwari-Pandey, R., Sairam, M.R. Carcinogenesis (2006) [Pubmed]
  40. Coordinate regulation by diethylstilbestrol of the platelet-derived growth factor-A (PDGF-A) and -B chains and the PDGF receptor alpha- and beta-subunits in the mouse uterus and vagina: potential mediators of estrogen action. Gray, K., Eitzman, B., Raszmann, K., Steed, T., Geboff, A., McLachlan, J., Bidwell, M. Endocrinology (1995) [Pubmed]
WikiGenes - Universities