Phosphorylated heterodimers of ERBB2 KD mutants and EGFR phosphorylate PLCG1

Stable Identifier
R-HSA-9665032
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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Phosphorylated heterodimers of ERBB2 KD mutants and EGFR phosphorylate PLCG1
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It is assumed that the following EGFR-binding ERBB2 mutants that were shown to activate PLCG1 (PLCgamma-1) signaling, evidenced by activating phosphorylation of PLCG1, recruit and phosphorylate PLCG1:

ERBB2 L755S (Bose et al. 2013);
ERBB2 I767M (Bose et al. 2013);
ERBB2 D769H (Bose et al. 2013);
ERBB2 D769Y (Bose et al. 2013);
ERBB2 V777L (Bose et al. 2013);
ERBB2 G778_P780dup (Bose et al. 2013);
ERBB2 V842I (Bose et al. 2013);
ERBB2 H878Y (Hu, Hu et al. 2015, Hu, Wan et al. 2015);
ERBB2 R896C (Bose et al. 2013);

It is assumed that, like the wild type ERBB2:EGFR heterodimer, phosphorylated heterodimers of these ERBB2 KD mutants and EGFR recruit PLCG1.

ERBB2 L755_T759del does not activate PLCG1 signaling (Bose et al. 2013).

Activation of PLCG1 downstream of the following PLCG1 mutants has not been studied and they are annotated as candidates:

ERBB2 L755M
ERBB2 L755W
ERBB2 D769N
ERBB2 V777M
ERBB2 V777E
ERBB2 V842E
ERBB2 H878R
ERBB2 R896H
Literature References
PubMed ID Title Journal Year
26375550 Tumor driven by gain-of-function HER2 H878Y mutant is highly sensitive to HER2 inhibitor

Hu, Z, Hu, Y, Liu, X, Xi, R, Zhang, A, Liu, D, Xie, Q, Chen, L

Oncotarget 2015
25853726 Phosphorylation of mutationally introduced tyrosine in the activation loop of HER2 confers gain-of-function activity

Hu, Z, Wan, X, Hao, R, Zhang, H, Li, L, Li, L, Xie, Q, Wang, P, Gao, Y, Chen, S, Wei, M, Luan, Z, Zhang, A, Huang, N, Chen, L

PLoS ONE 2015
23220880 Activating HER2 mutations in HER2 gene amplification negative breast cancer

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

Cancer Discov 2013
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR:PLCG1 [plasma membrane]

Physical Entity
p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR:PLCG1 [plasma membrane] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
Normal reaction
PLCG1 phosphorylation by p-EGFR:p-ERBB2 (Homo sapiens)
Functional status

Gain of function of p-6Y-ERBB2 KD mutants:EGF:p-6Y-EGFR:PLCG1 [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
Mondo
Authored
Orlic-Milacic, M  (2019-07-31)
Reviewed
Kancha, RK  (2019-09-16)
Created
Orlic-Milacic, M  (2019-10-28)
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