Heterodimers of ERBB2 ECD mutants and EGFR trans-autophosphorylate

Stable Identifier
R-HSA-9665389
Type
Reaction [transition]
Species
Homo sapiens
Compartment
plasma membrane, cytosol
ReviewStatus
5/5
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Heterodimers of ERBB2 ECD mutants and EGFR trans-autophosphorylate
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ERBB2 S310F shows stronger activation of downstream signaling than ERBB2 G309A and ERBB2 G309E, and is hyperphosphorylated on tyrosine residues in the C-tail (Greulich et al. 2012), while the C-tail phosphorylation of ERBB2 G309A (Bose et al. 2013) and ERBB2 G309E (Greulich et al. 2012) is comparable to the wild type ERBB2. Phosphorylation of EGFR was demonstrated in the presence of ERBB2 G309A (Bose et al. 2013). Except for ERBB2 C-tail tyrosine residues Y1221 and Y1222, which were shown to undergo trans-autophosphorylation in ERBB2 G309E, ERBB2 S310F and ERBB2 S310Y (Greulich et al. 2012), phosphorylation of specific tyrosine residues in ERBB2 and EGFR has not been examined and they are assumed to be the same as in the wild type ERBB2 heterodimers with EGFR.
Literature References
PubMed ID Title Journal Year
22908275 Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2

Walker, SR, Greulich, H, Pho, NH, Banerji, S, Berger, AH, Lawrence, MS, Getz, G, Frank, D, Tanaka, KE, Chen, TH, Mani, DR, Liao, R, Imielinski, M, Winckler, W, Lee, SH, Meyerson, M, Hahn, WC, Wong, KK, Ambrogio, L, Kaplan, B, Cho, J, Mertins, P, Carr, SA, Jaffe, JD, Zhang, X, Eck, MJ, Yun, CH, Zhang, J

Proc. Natl. Acad. Sci. U.S.A. 2012
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
Participants
Input
Output
Participates
as an event of
Catalyst Activity

protein tyrosine kinase activity of ERBB2 ECD mutants:EGF:EGFR [plasma membrane]

Physical Entity
ERBB2 ECD mutants:EGF:EGFR [plasma membrane] (Homo sapiens)
Activity
protein tyrosine kinase activity (GO:0004713)
This event is regulated
Negatively by
Regulator
ERBB2 ECD mutants:ERBIN:HSP90:CDC37:trastuzumab [plasma membrane] (Homo sapiens)
Active Unit
trastuzumab [extracellular region]
Regulator
ERBB2 ECD mutants:ERBIN:HSP90:CDC37:TKIs [plasma membrane] (Homo sapiens)
Active Unit
afatinib, neratinib, lapatinib [cytosol]
Normal reaction
Trans-autophosphorylation of ERBB2 heterodimers (Homo sapiens)
Functional status

Gain of function of ERBB2 ECD mutants:EGF:EGFR [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Orlic-Milacic, M  (2019-10-30)
Reviewed
Bose, R  (2019-10-25)
Kancha, RK  (2019-11-03)
Krishna, A  (2019-10-25)
Created
Orlic-Milacic, M  (2019-10-30)
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