Autophosphorylation of membrane-tethered fusions of PDGFRA or PDGFRB

Stable Identifier
Reaction [transition]
Homo sapiens
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Where they have been studied, transmembrane PDGFR fusion proteins have been shown to trans-autophosphorylate in a ligand-independent manner, stimulating downstream signaling and promoting oncogenic transformation (Carroll et al, 1996; Willbanks et al, 2000; Stover et al, 2006; Medves et al, 2010; Ozawa et al, 2010; reviewed in Wang et al, 2016; Appiah-Kubi et al, 2017). Many of the PDGFR fusions appear to signal through the STAT pathway, with some variability in which STAT family members are engaged. Other pathways activated downstream of the transmembrane fusions include MAP kinase, PLC gamma and PI3K signaling cascades (Medves et al, 2010; Ozawa et al, 2010; Willbanks et al, 2000; Carroll et al, 1996).

Literature References
PubMed ID Title Journal Year
27170215 The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are major players in oncogenesis, drug resistance, and attractive oncologic targets in cancer

Yao, X, Chen, Y, Wu, M, Qian, H, Wang, Y, Wu, Y, Appiah-Kubi, K

Growth Factors 2016
16690743 Activation of FIP1L1-PDGFRalpha requires disruption of the juxtamembrane domain of PDGFRalpha and is FIP1L1-independent

Marynen, P, Folens, C, Gilliland, DG, Williams, IR, Mentens, N, Cools, J, Stover, EH, Lee, BH, Chen, J

Proc. Natl. Acad. Sci. U.S.A. 2006
8962143 The TEL/platelet-derived growth factor beta receptor (PDGF beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF beta R kinase-dependent signaling pathways

Golub, TR, Gilliland, DG, Carroll, M, Tomasson, MH, Barker, GF

Proc. Natl. Acad. Sci. U.S.A. 1996
28010895 Platelet-derived growth factor receptors (PDGFRs) fusion genes involvement in hematological malignancies

Yao, X, Chen, Y, Wu, M, Qian, H, Wang, Y, Wu, Y, Appiah-Kubi, K, Lan, T

Crit. Rev. Oncol. Hematol. 2017
20889717 PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas

Ladanyi, M, Fomchenko, EI, Fujii, K, Brennan, CW, Tandon, A, Oka, H, Yasui, Y, Nakada, M, Wang, L, Sasayama, T, Holland, EC, Levine, RL, Pedraza, A, Utsuki, S, Huse, JT, Ozawa, T, Squatrito, M

Genes Dev. 2010
10812249 TEL/PDGFbetaR fusion protein activates STAT1 and STAT5: a common mechanism for transformation by tyrosine kinase fusion proteins

Gilliland, DG, Frank, DA, Carroll, M, Druker, BJ, Mahajan, S, Wilbanks, AM

Exp. Hematol. 2000
20164854 KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia

Duhoux, FP, Toffalini, F, Libouton, JM, Demoulin, JB, Poirel, HA, Medves, S, Ameye, G, Ferrant, A

Leukemia 2010
Catalyst Activity

protein tyrosine kinase activity of membrane-tethered PDGFR fusion dimers [plasma membrane]

Functional status

Gain of function of membrane-tethered PDGFR fusion dimers [plasma membrane]

Disease Entity
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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