Autophosphorylation of PDGF alpha receptors

Stable Identifier
Reaction [transition]
Homo sapiens
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Receptor dimerisation is key event in PDGF receptor activation. The intracellular regions of the receptors are juxtaposed which allows trans-phosphorylation between the two receptors in the complex.
The autophosphorylation site Y857 located inside the kinase domain of beta-receptor (PDGFRB) is important for activation of the kinase. This tyrosine is conserved in the alpha-receptor (PDGFRA), where it corresponsds to Y849, and in almost all other tyrosine kinase receptors. The other known autophosphorylation sites are localized outside the kinase domains of the alpha- and beta- receptors; of the 15( beta) or 16 (alpha) tyrosine residues in the intracellular, non-catalytic part of the beta- or alpha receptor, 11 and 10, respectively, are autophosphorylation sites (reviewed in Heldin et al, 1998).
PDGFRA and PDGFRB activity can be inhibited by binding to type I and type II tyrosine kinase inhibitors (reviewed in Roskoski, 2018). Type I inhibitors such as crenolanib, avripatinib and pazopanib, bind to the active conformation of the receptor and inhibit trans-autophosphorylation (Ip et al, 2018; Evans et al, 2017; Davids et al, 2009; reviewed in Roskoski, 2018; Klug et al, 2018; Papadopoulos and Lennartsson, 2016).

Literature References
PubMed ID Title Journal Year
30389923 Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies

Vellano, CP, Scott, KL, Ju, Z, Jeong, KJ, Shao, SH, Leonard, PG, Woessner, R, Mills, GB, Sahni, N, Ip, CKM, Hua, X, Ng, PKS

Nat Commun 2018
29408302 The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
9739761 Signal transduction via platelet-derived growth factor receptors

Ostman, A, Heldin, CH, Rönnstrand, L

Biochim Biophys Acta 1998
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Heinrich, MC, Kent, JD, Klug, LR

Pharmacol. Ther. 2018
29093181 A precision therapy against cancers driven by KIT/PDGFRA mutations

Heinrich, MC, Zhang, Y, Hodous, BL, Shutes, A, Lengauer, C, Evans, EK, Kohl, N, Wolf, B, Schöffski, P, Zhu, XJ, Kim, JL, Gebreyohannes, YK, Gardino, AK, Wozniak, A, DiPietro, L, Lydon, N, Wilson, K, Brooijmans, N, Schmidt-Kittler, O, Boral, A, Miller, S, LaBranche, TP, Deangelo, DJ, Davis, A, Guzi, T, Wilson, D

Sci Transl Med 2017
29137923 The PDGF/PDGFR pathway as a drug target

Lennartsson, J, Papadopoulos, N

Mol. Aspects Med. 2018
19564526 Response to a novel multitargeted tyrosine kinase inhibitor pazopanib in metastatic Merkel cell carcinoma

Chong, ML, Goh, BC, Hodge, J, Soong, R, Ng, SS, Davids, MS, Laubscher, K, Davids, M, Dar, M, Charlton, A

J. Clin. Oncol. 2009
Catalyst Activity

protein tyrosine kinase activity of PDGF alpha receptor: PDGF dimers [plasma membrane]

This event is regulated