RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR

Stable Identifier
R-HSA-9665707
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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RAS activation by SOS1 bound to phosphorylated heterodimers of ERBB2 TMD/JMD mutants and EGFR
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Activation of downstream RAS signaling was shown for ERBB2 S653C (de Martino et al. 2014) and ERBB2 R678Q (Bose et al. 2013, de Martino et al. 2014) through activating tyrosine phosphorylation on ERKs (MAPK1 and MAPK3). It is assumed that heterodimers of ERBB2 TMD/JMD mutants and EGFR, like the wild type ERBB2:EGFR heterodimers, directly bind to GRB:SOS1 complex, resulting in activation of RAS signaling to guanyl nucleotide exchange on RAS.
Literature References
PubMed ID Title Journal Year
24971884 Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinib

Rieken, M, Xylinas, E, Klatte, T, Shariat, SF, Rouprêt, M, Elemento, O, Clozel, T, Zhuang, D, Krzywinski, M, de Martino, M

Cancer Biol. Ther. 2014
23220880 Activating HER2 mutations in HER2 gene amplification negative breast cancer

Bose, R, Shen, W, Aronson, AB, Goel, N, Koboldt, DC, Li, S, Searleman, AC, Ma, CX, Ellis, MJ, Shen, D, Ding, L, Monsey, J, Mardis, ER, Kavuri, SM

Cancer Discov 2013
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Input
Output
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as an event of
Catalyst Activity

guanyl-nucleotide exchange factor activity of p-6Y-ERBB2 TMD/JMD mutants (RAS):EGF:p-6Y-EGFR:GRB2:SOS1 [plasma membrane]

Physical Entity
p-6Y-ERBB2 TMD/JMD mutants (RAS):EGF:p-6Y-EGFR:GRB2:SOS1 [plasma membrane] (Homo sapiens)
Activity
guanyl-nucleotide exchange factor activity (GO:0005085)
Normal reaction
RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and phosphorylated EGFR:ERBB2 heterodimers. (Homo sapiens)
Functional status

Gain of function of p-6Y-ERBB2 TMD/JMD mutants (RAS):EGF:p-6Y-EGFR:GRB2:SOS1 [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2019-10-31)
Reviewed
Bose, R  (2019-10-25)
Kancha, RK  (2019-11-03)
Krishna, A  (2019-10-25)
Created
Orlic-Milacic, M  (2019-10-31)
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