Signaling by cytosolic PDGFRA and PDGFRB fusion proteins

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R-HSA-9673766
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Pathway
Species
Homo sapiens
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In addition to activating missense mutations and in-frame deletions, PDGFRA and PDGFRB are also subject to gene fusion events arising from chromosomal rearrangements. PDGFR fusions often consist of the cytosolic domain of the receptor tyrosine kinase fused to the N-terminal oligomerization domain of an intracellular protein, leading to ligand-independent dimerization and constitutive activation (reviewed in Wang et al, 2016; Appiah-Kubi et al, 2017). To date there are about 35 identified PDGFR fusion partners, most of which form fusions with PDGFRB (reviewed in Appiah-Kubi et al, 2017). The most common cytosolic fusion partners of PDGFRA is FIP1L1, an RNA processing factor (Cools et al, 2003; Stover et al, 2006; Simon et al, 2008; Andrae et al, 2008; Ozawa et al, 2010; Appiah-Kubi et al, 2017). Fusion partners with PDGFRB are numerous but occurrence of these proteins is rare (Hidalgo-Curtis et al, 2010; reviewed in Wang et al, 2016; Appiah-Kubi et al, 2017).

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

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

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

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

Proc. Natl. Acad. Sci. U.S.A. 2006
12660384 A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome

Cools, J, Deangelo, DJ, Gotlib, J, Stover, EH, Legare, RD, Cortes, J, Kutok, J, Clark, J, Galinsky, I, Griffin, JD, Cross, NC, Tefferi, A, Malone, J, Alam, R, Schrier, SL, Schmid, J, Rose, M, Vandenberghe, P, Verhoef, G, Boogaerts, M, Wlodarska, I, Kantarjian, H, Marynen, P, Coutré, SE, Stone, R, Gilliland, DG

N. Engl. J. Med. 2003
18483217 Role of platelet-derived growth factors in physiology and medicine

Andrae, J, Gallini, R, Betsholtz, C

Genes Dev 2008
18234315 Primary resistance to imatinib in Fip1-like 1-platelet-derived growth factor receptor alpha-positive eosinophilic leukemia

Simon, D, Salemi, S, Yousefi, S, Simon, HU

J. Allergy Clin. Immunol. 2008
28010895 Platelet-derived growth factor receptors (PDGFRs) fusion genes involvement in hematological malignancies

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

Crit. Rev. Oncol. Hematol. 2017
20085582 Fusion of PDGFRB to two distinct loci at 3p21 and a third at 12q13 in imatinib-responsive myeloproliferative neoplasms

Hidalgo-Curtis, C, Apperley, JF, Stark, A, Stark, A, Jeng, M, Gotlib, J, Chase, A, Cross, NC, Grand, FH

Br. J. Haematol. 2010
20889717 PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas

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

Genes Dev. 2010
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cancer 162 malignant tumor, malignant neoplasm, primary cancer
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