Platelet-derived growth factor receptor alpha
From Ganfyd
PDGFRA (PDGFRα) is important as a type III receptor tyrosine kinase with mutations associated with various tumours, notably GIST, but also haematological maligancies and gliomas. A common mutation at exon 18 (Asp842Val) causes imatinib resistance[1]. The FIP1L1-PDGFRA fusion tyrosine kinase is associated with idiopathic hypereosinophilic syndrome (HES) that is poorly responsive to steroids and chronic eosinophilic leukaemia (CEL)[2]. PDGFRA mutation is uncommon in most human cancers[3]. Expression may predict survival in renal cancer[4]. The receptor protein has a role in antiapoptotic signaling and body repair, activation being associated with collagen deposition[5]. There appears to be an association of some haplotypes with congenital neural tube defects[6].
Platelet-derived growth factor receptor α dependent cell survival seems to be mainly mediated through activation of phosphatidylinositol 3'-kinase (PI3K) and negatively regulated by the Src family kinases[7].
It is coded for at 4q12 and the gene contains 23 exons spanning about 65 kb.
References
- ↑ Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Seminars in diagnostic pathology 2006;23(2):91-102.
- ↑ Gotlib J, Cools J, Malone JM, Schrier SL, Gilliland DG, Coutré SE. The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood 2004;103(8):2879-91. (Direct link – subscription may be required.)
- ↑ Sihto H, Sarlomo-Rikala M, Tynninen O, Tanner M, Andersson LC, Franssila K, et al. KIT and platelet-derived growth factor receptor alpha tyrosine kinase gene mutations and KIT amplifications in human solid tumors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005;23(1):49-57. (Direct link – subscription may be required.)
- ↑ Tawfik OW, Kramer B, Shideler B, Danley M, Kimler BF, Holzbeierlein J. Prognostic significance of CD44, platelet-derived growth factor receptor alpha, and cyclooxygenase 2 expression in renal cell carcinoma. Archives of pathology & laboratory medicine 2007;131(2):261-7.
- ↑ Zymek P, Bujak M, Chatila K, Cieslak A, Thakker G, Entman ML, et al. The role of platelet-derived growth factor signaling in healing myocardial infarcts. Journal of the American College of Cardiology 2006;48(11):2315-23. (Direct link – subscription may be required.)
- ↑ Joosten PH, Toepoel M, Mariman EC, Van Zoelen EJ. Promoter haplotype combinations of the platelet-derived growth factor alpha-receptor gene predispose to human neural tube defects. Nature genetics 2001;27(2):215-7. (Direct link – subscription may be required.)
- ↑ Vantler M, Huntgeburth M, Caglayan E, Ten Freyhaus H, Schnabel P, Rosenkranz S. PI3-kinase/Akt-dependent antiapoptotic signaling by the PDGF alpha receptor is negatively regulated by Src family kinases. FEBS letters 2006;580(30):6769-76. (Direct link – subscription may be required.)
