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Gene Review

PDGFA  -  platelet-derived growth factor alpha...

Homo sapiens

Synonyms: PDGF subunit A, PDGF-1, PDGF-A, PDGF1, Platelet-derived growth factor A chain, ...
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Disease relevance of PDGFA


Psychiatry related information on PDGFA

  • These findings of the inappropriate coexpression of a potent mitogen, PDGF, and its receptor in lung cancer epithelial cells suggest the presence of a powerful in vivo mechanism contributing to the self-stimulation and unregulated growth of lung cancer tumor cells [6].
  • We suggest that a local impairment of the PDGF/PDGFR system may contribute to CC fibrosis, which is an established cause of erectile dysfunction in man [7].
  • In contrast, increased PDGF-A expression in vivo increases tumor incidence and growth rate and decreases the latency period to tumor formation whereas abrogation of PDGF-A expression decreases tumor incidence and increases latency [8].
  • However, the response latency seen with both PDGF and EGF was greater for senescent cells [9].
  • This critical period comprised the interval of approximately 10-20 h after PDGF addition and especially the early part of this interval [10].

High impact information on PDGFA


Chemical compound and disease context of PDGFA

  • The effects of PDGF/IL-1beta costimulation on contractile marker expression and Akt and p70S6K phosphorylation were blocked by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 and by adenovirus expressing a dominant-negative Akt, and they were mimicked by constitutively active Akt [12].
  • The functional significance of PDGF autocrine signaling in these cells was demonstrated by the fact that the CT52923 inhibited soft agar colony formation, and, when given p.o. to nude mice, it effectively reduced tumor formation by 44% (P < 0.0019) after s.c. injection of C6 glioblastoma cells [13].
  • Imatinib mesylate is also a potent inhibitor of the PDGF-R kinase and is currently being evaluated for the treatment of PDGF-responsive tumors such as prostate cancer [14].
  • PURPOSE: To test the hypothesis that progression of androgen sensitive prostate cancer is dependent on growth factors, such as platelet derived growth factor (PDGF), and inhibition of PDGF receptor (PDGF-R) with imatinib will induce anti-tumor activity [15].
  • Preoperative administration of GnRH-a plus tibolone to premenopausal women with uterine fibroids: evaluation of the clinical response, the immunohistochemical expression of PDGF, bFGF and VEGF and the vascular pattern [16].

Biological context of PDGFA


Anatomical context of PDGFA


Associations of PDGFA with chemical compounds

  • Also, angiotensin II induced expression of KLF5, which in turn activated platelet-derived growth factor-A (PDGF-A) and transforming growth factor-beta (TGF-beta) expression [26].
  • The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors [27].
  • The APP-Gal4 processing induced by PDGF is dependent on the gamma-secretase activity, being abolished by an inhibitor of this enzyme, and is the consequence of the activation of a pathway downstream of the PDGF-receptor, which includes the non-receptor tyrosine kinase Src and the small G-protein Rac1 [28].
  • Immunohistochemistry was correlated with in situ hybridization on adjacent, formalin fixed tissue sections from nephrectomies utilizing riboprobes made from PDGF-A and -B chain cDNA [29].
  • Significant correlations were observed between the urinary protein level and the mRNA level of PDGF-beta receptor expression and PDGF B-chain expression, and between the serum creatinine level and the mRNA level of PDGF-beta receptor expression [30].

Physical interactions of PDGFA

  • They do not however, exclude other domains of the PDGF A or B chains as additional binding sites for heparin nor do they exclude the possibility that heparin and the PDGF receptor share a common binding site [31].
  • Chromatin immunoprecipitation assay showed KLF5/BTEB2 to be induced and to bind the promoter of the PDGF-A gene in response to angiotensin II stimulation [32].
  • METHODS: Purified TSP-1 was analyzed for bound PDGF [33].
  • A chimeric receptor consisting of an epidermal growth factor (EGF) receptor ligand-binding domain and platelet-derived growth factor (PDGF) receptor transmembrane and cytoplasmic signalling domains has been constructed and shown to be fully functional in phosphorylation, mitogenesis, transformation, Ca2+ release, and pH change assays [34].
  • Similar results were obtained with 125I-PDGF isoforms binding to immobilized bovine alpha 2M and alpha 2M-methylamine [35].

Enzymatic interactions of PDGFA

  • Our data indicate that S6 kinase is recruited into a complex with RTKs and src and becomes phosphorylated on tyrosine/s in response to PDGF or serum [36].
  • Third, those fusion proteins that associated with the PDGF receptor also became phosphorylated in vivo following PDGF treatment, and in in vitro kinase assays, suggesting that the amino-terminal half of Fyn contains the sites of PDGF-stimulated phosphorylation [37].
  • Previously, it had been shown that PLC-gamma 1 was phosphorylated on tyrosine residues by the agonist-occupied platelet-derived growth factor (PDGF) receptor and epidermal growth factor (EGF) receptor in cells other than platelets [38].

Co-localisations of PDGFA

  • Double-label assays showed that PDGFR beta was often colocalized with each PDGF ligand, especially in pigmented cells [39].

Regulatory relationships of PDGFA


Other interactions of PDGFA

  • We describe here a procedure for the preparation of homogeneous ODGF, and provide evidence that this factor, which binds to the PDGF receptor, has a structure similar to a homodimer of PDGF A-chains [45].
  • Furthermore, anti-PDGF antibody partially abrogates the mitogenic effect of EGF, suggesting that mitogen-stimulated PDGF synthesis in mesangial cells is at least partly responsible for cell growth induced by other growth factors [40].
  • Rat skeletal myoblasts and arterial smooth muscle cells express the gene for the A chain but not the gene for the B chain (c-sis) of platelet-derived growth factor (PDGF) and produce a PDGF-like protein [46].
  • Unlike in several other cells, exogenously added TGF-beta 1 or 2 affected neither TGF-beta nor PDGF RNA expression in K562 cells [47].
  • Expression of mRNA-encoding transforming growth factors alpha and beta (TGF alpha and beta), epidermal growth factor receptor (EGFR), and platelet-derived growth factors (PDGF) A and B chains was examined in 63 human gastric biopsies [48].

Analytical, diagnostic and therapeutic context of PDGFA


  1. Negative trans-acting mechanisms controlling expression of platelet-derived growth factor A and B MRNA in somatic cell hybrids. Levéen, P., Betsholtz, C., Westermark, B. Exp. Cell Res. (1993) [Pubmed]
  2. Molecular analysis of genomic abnormalities in human gliomas. Bello, M.J., de Campos, J.M., Kusak, M.E., Vaquero, J., Sarasa, J.L., Pestaña, A., Rey, J.A. Cancer Genet. Cytogenet. (1994) [Pubmed]
  3. Rapid reversion of Loeffler's endocarditis by imatinib in early stage clonal hypereosinophilic syndrome. Rotoli, B., Catalano, L., Galderisi, M., Luciano, L., Pollio, G., Guerriero, A., D'Errico, A., Mecucci, C., La Starza, R., Frigeri, F., Di Francia, R., Pinto, A. Leuk. Lymphoma (2004) [Pubmed]
  4. Molecular characterization of PDGFR-alpha/PDGF-A and c-KIT/SCF in gliosarcomas. Reis, R.M., Martins, A., Ribeiro, S.A., Basto, D., Longatto-Filho, A., Schmitt, F.C., Lopes, J.M. Cellular oncology : the official journal of the International Society for Cellular Oncology. (2005) [Pubmed]
  5. Production of platelet-derived growth factor-like mitogen by smooth-muscle cells from human atheroma. Libby, P., Warner, S.J., Salomon, R.N., Birinyi, L.K. N. Engl. J. Med. (1988) [Pubmed]
  6. Malignant epithelial cells in primary human lung carcinomas coexpress in vivo platelet-derived growth factor (PDGF) and PDGF receptor mRNAs and their protein products. Antoniades, H.N., Galanopoulos, T., Neville-Golden, J., O'Hara, C.J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. Platelet-derived growth factor (PDGF) and PDGF receptors in rat corpus cavernosum: changes in expression after transient in vivo hypoxia. Aversa, A., Basciani, S., Visca, P., Arizzi, M., Gnessi, L., Frajese, G., Fabbri, A. J. Endocrinol. (2001) [Pubmed]
  8. Paradoxical effects of platelet-derived growth factor-A overexpression in malignant mesothelioma. Antiproliferative effects in vitro and tumorigenic stimulation in vivo. Metheny-Barlow, L.J., Flynn, B., van Gijssel, H.E., Marrogi, A., Gerwin, B.I. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  9. IP(3), IP(3) receptor, and cellular senescence. Huang, M.S., Adebanjo, O.A., Awumey, E., Biswas, G., Koval, A., Sodam, B.R., Sun, L., Moonga, B.S., Epstein, J., Goldstein, S., Lai, F.A., Lipschitz, D., Zaidi, M. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  10. Relationship between mevalonate and mitogenesis in human fibroblasts stimulated with platelet-derived growth factor. Fairbanks, K.P., Witte, L.D., Goodman, D.S. J. Biol. Chem. (1984) [Pubmed]
  11. Mechanism of action and in vivo role of platelet-derived growth factor. Heldin, C.H., Westermark, B. Physiol. Rev. (1999) [Pubmed]
  12. Synergistic roles of platelet-derived growth factor-BB and interleukin-1beta in phenotypic modulation of human aortic smooth muscle cells. Chen, C.N., Li, Y.S., Yeh, Y.T., Lee, P.L., Usami, S., Chien, S., Chiu, J.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  13. Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Lokker, N.A., Sullivan, C.M., Hollenbach, S.J., Israel, M.A., Giese, N.A. Cancer Res. (2002) [Pubmed]
  14. Platelet-derived growth factor receptors: a therapeutic target in solid tumors. George, D. Semin. Oncol. (2001) [Pubmed]
  15. A phase II trial of imatinib mesylate in patients with prostate specific antigen progression after local therapy for prostate cancer. Rao, K., Goodin, S., Levitt, M.J., Dave, N., Shih, W.J., Lin, Y., Capanna, T., Doyle-Lindrud, S., Juvidian, P., DiPaola, R.S. Prostate (2005) [Pubmed]
  16. Preoperative administration of GnRH-a plus tibolone to premenopausal women with uterine fibroids: evaluation of the clinical response, the immunohistochemical expression of PDGF, bFGF and VEGF and the vascular pattern. Di Lieto, A., De Falco, M., Mansueto, G., De Rosa, G., Pollio, F., Staibano, S. Steroids (2005) [Pubmed]
  17. Hepatocyte growth factor/scatter factor differentially regulates expression of proangiogenic factors through Egr-1 in head and neck squamous cell carcinoma. Worden, B., Yang, X.P., Lee, T.L., Bagain, L., Yeh, N.T., Cohen, J.G., Van Waes, C., Chen, Z. Cancer Res. (2005) [Pubmed]
  18. Human PDGFA receptor gene maps to the same region on chromosome 4 as the KIT oncogene. Stenman, G., Eriksson, A., Claesson-Welsh, L. Genes Chromosomes Cancer (1989) [Pubmed]
  19. Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression. Langerak, A.W., Williamson, K.A., Miyagawa, K., Hagemeijer, A., Versnel, M.A., Hastie, N.D. Genes Chromosomes Cancer (1995) [Pubmed]
  20. Platelet-derived growth factor A chain: confirmation of localization of PDGFA to chromosome 7p22 and description of an unusual minisatellite. Bonthron, D., Collins, T., Grzeschik, K.H., van Roy, N., Speleman, F. Genomics (1992) [Pubmed]
  21. Interleukin-1 in myocardium and coronary arteries of patients with dilated cardiomyopathy. Francis, S.E., Holden, H., Holt, C.M., Duff, G.W. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  22. Induction of growth factor RNA expression in human malignant melanoma: markers of transformation. Albino, A.P., Davis, B.M., Nanus, D.M. Cancer Res. (1991) [Pubmed]
  23. Tumor-Driven Paracrine Platelet-Derived Growth Factor Receptor {alpha} Signaling Is a Key Determinant of Stromal Cell Recruitment in a Model of Human Lung Carcinoma. Tejada, M.L., Yu, L., Dong, J., Jung, K., Meng, G., Peale, F.V., Frantz, G.D., Hall, L., Liang, X., Gerber, H.P., Ferrara, N. Clin. Cancer Res. (2006) [Pubmed]
  24. Molecular and Biochemical Analyses of Platelet-Derived Growth Factor Receptor (PDGFR) B, PDGFRA, and KIT Receptors in Chordomas. Tamborini, E., Miselli, F., Negri, T., Lagonigro, M.S., Staurengo, S., Dagrada, G.P., Stacchiotti, S., Pastore, E., Gronchi, A., Perrone, F., Carbone, A., Pierotti, M.A., Casali, P.G., Pilotti, S. Clin. Cancer Res. (2006) [Pubmed]
  25. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Collins, T., Ginsburg, D., Boss, J.M., Orkin, S.H., Pober, J.S. Nature (1985) [Pubmed]
  26. Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling. Shindo, T., Manabe, I., Fukushima, Y., Tobe, K., Aizawa, K., Miyamoto, S., Kawai-Kowase, K., Moriyama, N., Imai, Y., Kawakami, H., Nishimatsu, H., Ishikawa, T., Suzuki, T., Morita, H., Maemura, K., Sata, M., Hirata, Y., Komukai, M., Kagechika, H., Kadowaki, T., Kurabayashi, M., Nagai, R. Nat. Med. (2002) [Pubmed]
  27. The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Raines, E.W., Lane, T.F., Iruela-Arispe, M.L., Ross, R., Sage, E.H. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  28. Platelet-derived growth factor induces the beta-gamma-secretase-mediated cleavage of Alzheimer's amyloid precursor protein through a Src-Rac-dependent pathway. Gianni, D., Zambrano, N., Bimonte, M., Minopoli, G., Mercken, L., Talamo, F., Scaloni, A., Russo, T. J. Biol. Chem. (2003) [Pubmed]
  29. Identification of platelet-derived growth factor A and B chains in human renal vascular rejection. Alpers, C.E., Davis, C.L., Barr, D., Marsh, C.L., Hudkins, K.L. Am. J. Pathol. (1996) [Pubmed]
  30. Expression of PDGF and PDGF receptor mRNA in glomeruli in IgA nephropathy. Terada, Y., Yamada, T., Nakashima, O., Sasaki, S., Nonoguchi, H., Tomita, K., Marumo, F. J. Am. Soc. Nephrol. (1997) [Pubmed]
  31. Heparin-like glycosaminoglycans influence growth and phenotype of human arterial smooth muscle cells in vitro. II. The platelet-derived growth factor A-chain contains a sequence that specifically binds heparin. Fager, G., Camejo, G., Olsson, U., Ostergren-Lundén, G., Bondjers, G. In Vitro Cell. Dev. Biol. (1992) [Pubmed]
  32. KLF5/BTEB2, a Krüppel-like zinc-finger type transcription factor, mediates both smooth muscle cell activation and cardiac hypertrophy. Nagai, R., Shindo, T., Manabe, I., Suzuki, T., Kurabayashi, M. Adv. Exp. Med. Biol. (2003) [Pubmed]
  33. Thrombospondin-1 promotes proliferative healing through stabilization of PDGF. Krishnaswami, S., Ly, Q.P., Rothman, V.L., Tuszynski, G.P. J. Surg. Res. (2002) [Pubmed]
  34. Analysis of platelet-derived growth factor receptor domain function using a novel chimeric receptor approach. Seedorf, K., Felder, S., Millauer, B., Schlessinger, J., Ullrich, A. J. Biol. Chem. (1991) [Pubmed]
  35. Differential binding and regulation of platelet-derived growth factor A and B chain isoforms by alpha 2-macroglobulin. Bonner, J.C., Osornio-Vargas, A.R. J. Biol. Chem. (1995) [Pubmed]
  36. Receptor association and tyrosine phosphorylation of S6 kinases. Rebholz, H., Panasyuk, G., Fenton, T., Nemazanyy, I., Valovka, T., Flajolet, M., Ronnstrand, L., Stephens, L., West, A., Gout, I.T. FEBS J. (2006) [Pubmed]
  37. Association of Fyn with the activated platelet-derived growth factor receptor: requirements for binding and phosphorylation. Twamley, G.M., Kypta, R.M., Hall, B., Courtneidge, S.A. Oncogene (1992) [Pubmed]
  38. Thrombin activation of human platelets causes tyrosine phosphorylation of PLC-gamma 2. Tate, B.F., Rittenhouse, S.E. Biochim. Biophys. Acta (1993) [Pubmed]
  39. Platelet-derived growth factor ligands and receptors immunolocalized in proliferative retinal diseases. Robbins, S.G., Mixon, R.N., Wilson, D.J., Hart, C.E., Robertson, J.E., Westra, I., Planck, S.R., Rosenbaum, J.T. Invest. Ophthalmol. Vis. Sci. (1994) [Pubmed]
  40. Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens. Silver, B.J., Jaffer, F.E., Abboud, H.E. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  41. Expression of multiple growth factors in a human lung cancer cell line. Betsholtz, C., Bergh, J., Bywater, M., Pettersson, M., Johnsson, A., Heldin, C.H., Ohlsson, R., Knott, T.J., Scott, J., Bell, G.I. Int. J. Cancer (1987) [Pubmed]
  42. Inhibition of growth factor-mediated tyrosine phosphorylation in vascular smooth muscle by PD 089828, a new synthetic protein tyrosine kinase inhibitor. Dahring, T.K., Lu, G.H., Hamby, J.M., Batley, B.L., Kraker, A.J., Panek, R.L. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  43. Epigallocatechin-3-gallate inhibits the PDGF-induced VEGF expression in human vascular smooth muscle cells via blocking PDGF receptor and Erk-1/2. Park, J.S., Kim, M.H., Chang, H.J., Kim, K.M., Kim, S.M., Shin, B.A., Ahn, B.W., Jung, Y.D. Int. J. Oncol. (2006) [Pubmed]
  44. Specific inhibition of human skin fibroblast chemotaxis to platelet-derived growth factor A-chain homodimer by transforming growth factor-beta1. Soma, Y., Mizoguchi, M., Yamane, K., Yazawa, N., Kubo, M., Ihn, H., Kikuchi, K., Tamaki, K. Arch. Dermatol. Res. (2002) [Pubmed]
  45. A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains. Heldin, C.H., Johnsson, A., Wennergren, S., Wernstedt, C., Betsholtz, C., Westermark, B. Nature (1986) [Pubmed]
  46. Rat skeletal myoblasts and arterial smooth muscle cells express the gene for the A chain but not the gene for the B chain (c-sis) of platelet-derived growth factor (PDGF) and produce a PDGF-like protein. Sejersen, T., Betsholtz, C., Sjölund, M., Heldin, C.H., Westermark, B., Thyberg, J. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  47. Enhanced expression of transforming growth factor beta during megakaryoblastic differentiation of K562 leukemia cells. Alitalo, R., Mäkelä, T.P., Koskinen, P., Andersson, L.C., Alitalo, K. Blood (1988) [Pubmed]
  48. Expression of growth factor and epidermal growth factor receptor encoded transcripts in human gastric tissues. Bennett, C., Paterson, I.M., Corbishley, C.M., Luqmani, Y.A. Cancer Res. (1989) [Pubmed]
  49. Human melanoma cell lines of primary and metastatic origin express the genes encoding the chains of platelet-derived growth factor (PDGF) and produce a PDGF-like growth factor. Westermark, B., Johnsson, A., Paulsson, Y., Betsholtz, C., Heldin, C.H., Herlyn, M., Rodeck, U., Koprowski, H. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  50. Structural characterization of the human platelet-derived growth factor A-chain cDNA and gene: alternative exon usage predicts two different precursor proteins. Rorsman, F., Bywater, M., Knott, T.J., Scott, J., Betsholtz, C. Mol. Cell. Biol. (1988) [Pubmed]
  51. Expression of recombinant platelet-derived growth factor A- and B-chain homodimers in rat-1 cells and human fibroblasts reveals differences in protein processing and autocrine effects. Bywater, M., Rorsman, F., Bongcam-Rudloff, E., Mark, G., Hammacher, A., Heldin, C.H., Westermark, B., Betsholtz, C. Mol. Cell. Biol. (1988) [Pubmed]
  52. Expression of platelet-derived growth factor and its receptors in neuroendocrine tumors of the digestive system. Chaudhry, A., Papanicolaou, V., Oberg, K., Heldin, C.H., Funa, K. Cancer Res. (1992) [Pubmed]
  53. Platelet-derived growth factor C (PDGF-C), a novel growth factor that binds to PDGF alpha and beta receptor. Gilbertson, D.G., Duff, M.E., West, J.W., Kelly, J.D., Sheppard, P.O., Hofstrand, P.D., Gao, Z., Shoemaker, K., Bukowski, T.R., Moore, M., Feldhaus, A.L., Humes, J.M., Palmer, T.E., Hart, C.E. J. Biol. Chem. (2001) [Pubmed]
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