Signaling by PDGFR in disease

Stable Identifier
R-HSA-9671555
Type
Pathway
Species
Homo sapiens
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PDGFRA and PDGFRB are type III receptor tyrosine kinases that promote development and maintenance of mesenchymal tissues, including vascular smooth muscle, kidney, intestine, skin and lung, among others (reviewed in Tallquist and Kazlauskas, 2004; reviewed in Wang et al, 2016). Signaling through PDGF receptors stimulates cell proliferation and survival through activation of downstream signaling pathways including the RAS-MAP kinase cascade, PI3K signaling and STAT signaling (reviewed in Roskoski, 2018). Aberrant signaling through PDGF receptors is implicated in a number of human diseases. Point mutations in PDGFRA and, to a lesser extent, PDGFRB are implicated in a number of cancers, such as gastrointestinal stromal tumors (GIST; 5-10% mutation frequency in PDGFRA) and haematological cancers (Corless et al, 2005; Wang et al, 2016; reviewed in Klug et al, 2018). In addition, amplified signaling through the PDGF pathway can arise through gene fusion events or overexpression of ligand or receptor through gene amplification (Ozawa et al, 2010; Verhaak et al, 2010; reviewed in Appiah-Kubi et al, 2017).

Literature References
PubMed ID Title Journal Year
20129251 Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1

Verhaak, RG, Hoadley, KA, Purdom, E, Wang, V, Qi, Y, Wilkerson, MD, Miller, CR, Ding, L, Golub, T, Mesirov, JP, Alexe, G, Lawrence, M, O'Kelly, M, Tamayo, P, Weir, BA, Gabriel, S, Winckler, W, Gupta, S, Jakkula, L, Feiler, HS, Hodgson, JG, James, CD, Sarkaria, JN, Brennan, C, Kahn, A, Spellman, PT, Wilson, RK, Speed, TP, Gray, JW, Meyerson, M, Getz, G, Perou, CM, Hayes, DN, Cancer Genome Atlas Research Network, -

Cancer Cell 2010
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
29408302 The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
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
15207812 PDGF signaling in cells and mice

Tallquist, M, Kazlauskas, A

Cytokine Growth Factor Rev. 2004
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Klug, LR, Kent, JD, Heinrich, MC

Pharmacol. Ther. 2018
15928335 PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib

Corless, CL, Schroeder, A, Griffith, D, Town, A, McGreevey, L, Harrell, P, Shiraga, S, Bainbridge, T, Morich, J, Heinrich, MC

J. Clin. Oncol. 2005
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
Participants
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Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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