Autophosphorylation of PDGFR mutant dimers

Stable Identifier
R-HSA-9672175
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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Autophosphorylation of PDGFR mutant dimers
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Activating mutations in the kinase, juxtamembrane and transmembrane domains of PDGFRA lead to constitutive, ligand-independent dimerization and trans-autophosphorylation, and stimulate downstream signaling pathways (Heinrich et al, 2003; Hirota et al, 2003; Corless et al, 2005; Velghe et al, 2014; reviewed in Roskoski et al, 2018; Klug et al, 2018).
Literature References
PubMed ID Title Journal Year
29408302 The role of small molecule platelet-derived growth factor receptor (PDGFR) inhibitors in the treatment of neoplastic disorders

Roskoski, R

Pharmacol. Res. 2018
12522257 PDGFRA activating mutations in gastrointestinal stromal tumors

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

Science 2003
12949711 Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors

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

Gastroenterology 2003
29964125 Structural and clinical consequences of activation loop mutations in class III receptor tyrosine kinases

Heinrich, MC, Kent, JD, Klug, LR

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

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

J. Clin. Oncol. 2005
23752188 PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations

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

Oncogene 2014
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of PDGFR mutant dimers [plasma membrane]

Physical Entity
PDGFR mutant dimers [plasma membrane] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
Normal reaction
Autophosphorylation of PDGF alpha receptors (Homo sapiens)
Functional status

Gain of function of PDGFR mutant dimers [plasma membrane]

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