GRB2:SOS1 complex binds to mutant PDGFR receptor

Stable Identifier
R-HSA-9672164
Type
Reaction [binding]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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GRB2:SOS1 complex binds to mutant PDGFR receptor
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MAP kinase signaling is activated downstream of gain-of-function missense and in-frame deletion PDGFRA mutants, as assessed by increased levels of phosphorylated MAPK3 and MAPK1 proteins (ERK1 and ERK2, respectively) (Heinrich et al, 2003; Corless et al, 2005; Ohashi et al, 2004; Velghe et al, 2014). RAS and MAPK activation is assumed to occur through the recruitment of GRB2:SOS1 to phosphorylated T720, as is the case for the wild-type receptor, although this has not been conclusively demonstrated (Bazenet et al, 1996; reviewed in Corless et al, 2011; Roskoski, 2018).
Literature References
PubMed ID Title Journal Year
22089421 Gastrointestinal stromal tumours: origin and molecular oncology

Corless, CL, Barnett, CM, Heinrich, MC

Nat. Rev. Cancer 2011
29408302 The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
15221957 Different inhibitory effect of imatinib on phosphorylation of mitogen-activated protein kinase and Akt and on proliferation in cells expressing different types of mutant platelet-derived growth factor receptor-alpha

Ohashi, A, Kinoshita, K, Isozaki, K, Nishida, T, Shinomura, Y, Kitamura, Y, Hirota, S

Int. J. Cancer 2004
12522257 PDGFRA activating mutations in gastrointestinal stromal tumors

Heinrich, MC, Corless, CL, Duensing, A, McGreevey, L, Chen, CJ, Joseph, N, Singer, S, Griffith, DJ, Haley, A, Town, A, Demetri, GD, Fletcher, CD, Fletcher, JA

Science 2003
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
8943348 Phosphorylation of tyrosine 720 in the platelet-derived growth factor alpha receptor is required for binding of Grb2 and SHP-2 but not for activation of Ras or cell proliferation

Bazenet, CE, Gelderloos, JA, Kazlauskas, A

Mol. Cell. Biol. 1996
23752188 PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations

Velghe, AI, Van Cauwenberghe, S, Polyansky, AA, Chand, D, Montano-Almendras, CP, Charni, S, Hallberg, B, Essaghir, A, Demoulin, JB

Oncogene 2014
Participants
Input
Output
Participates
as an event of
Normal reaction
GRB2:SOS1 complex binds to the active receptor (Homo sapiens)
Functional status

Gain of function of p-11Y PDGFR mutant receptor dimers [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
Mondo
Authored
Rothfels, K  (2020-02-25)
Reviewed
Ip, CKM  (2020-02-06)
Created
Rothfels, K  (2019-12-23)
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