ERBB2 KD mutants heterodimerize

Stable Identifier
R-HSA-9664567
Type
Reaction [dissociation]
Species
Homo sapiens
Compartment
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The following ERBB2 KD mutants were directly or indirectly shown to form heterodimers with EGFR:

ERBB2 L755P (Kancha et al. 2011 – indirect, higher catalytic activity in the presence of EGF stimulated EGFR);
ERBB2 L755S (Kancha et al. 2011, Bose et al. 2013 – indirect, higher kinase activity in the presence of EGFR);
ERBB2 I767M (Bose et al. 2013 – indirect, EGFR is phosphorylated in the presence of ERBB2 I767M);
ERBB2 D769H (Bose et al. 2013 – indirect, trans autophosphorylation in the presence of EGFR);
ERBB2 D769Y (Bose et al. 2013 – indirect, trans autophosphorylation in the presence of EGFR);
ERBB2 V777L (Kancha et al. 2011, Bose et al. 2013 – indirect, increased catalytic activity in the presence of EGF activated EGFR);
ERBB2 P780_Y781insGSP (Bose et al. 2013, Suzawa et al. 2016, Ogoshi et al. 2019 – indirect, trans-autophosphorylates in the presence of EGFR);
ERBB2 T798M (Kancha et al. 2011, Rexer et al. 2013 – indirect, trans-autophosphorylation in the presence of EGF-stimulated EGFR);
ERBB2 V842I (Bose et al. 2013 – indirect, trans-autophosphorylation in the presence of EGFR);
ERBB2 T862A (Kancha et al. 2011 –indirect, increased catalytic activity in the presence of EGF activated EGFR);
ERBB2 H878Y (Kancha et al. 2011 – indirect, activated in the presence of EGF-stimulated EGFR);
ERBB2 R896C (Bose et al. 2013 – indirect, trans autophosphorylation in the presence of EGFR);
ERBB2 L755_T759del (Bose et al. 2013 – indirect, EGFR phosphorylated in the presence of the mutant);
ERBB2 A775_G776insYVMA (Wang et al. 2006 - direct)

The following ERBB2 KD mutants were directly or indirectly shown to form heterodimers with ERBB3:

ERBB2 L755P (Kancha et al. 2011 – indirect, higher catalytic activity in the presence of neuregulin stimulated ERBB3);
ERBB2 L755S (Croessmann et al. 2019 – direct, mutant forms heterodimers with ERBB3 at a higher rate than the wild type ERBB2; Kancha et al. 2011, Bose et al. 2013 – indirect, higher kinase activity in the presence of ERBB3);
ERBB2 I767M (Ng et al. 2015 – indirect, catalytic activity induced by neuregulin-1 (NRG1));
ERBB2 D769H (Collier al. 2013 – direct, 3-fold increase in catalytic activity upon heterodimerization);
ERBB2 D769Y (Collier al. 2013 – direct, 3-fold increase in catalytic activity upon heterodimerization);
ERBB2 G776S (Fan et al. 2008 – indirect, trans-autophosphorylation increased in the presence of the mutant);
ERBB2 V777L (Croessmann et al. 2019 – direct, mutant forms heterodimers with ERBB3 at a higher rate than the wild type ERBB2; Kancha et al. 2011, Bose et al. 2013 – indirect, increased catalytic activity in the presence of neuregulin-activated ERBB3);
ERBB2 T798M (Rexer et al. 2013 – direct, co-immunoprecipitates with ERBB3; Kancha et al. 2011, Rexer et al. 2013 – indirect, trans-autophosphorylation in the presence of neuregulin-stimulated ERBB3);
ERBB2 V842I (Bose et al. 2013 – indirect, trans-autophosphorylation in the presence of ERBB3);
ERBB2 T862A (Kancha et al. 2011 - indirect, increased catalytic activity in the presence of neuregulin-activated ERBB3);
ERBB2 L869R (Hanker et al. 2017 – direct, heterodimerization may be increased in the presence of ERBB3 E928G mutant);
ERBB2 H878Y (Kancha et al. 2011 – indirect, activated in the presence of neuregulin-stimulated ERBB3);
ERBB2 L755_T759del (Bose et al. 2013 – indirect, ERBB3 phosphorylated in the presence of the mutant);
ERBB2 A775_G776insYVMA (Wang et al. 2006 - direct)

Heterodimerizaton of ERBB2 KD mutants with ERBB4 has not been tested and ERBB4 is shown as a heterodimerization candidate.

Heterodimerization properties of the following ERBB2 KD mutants have not been tested and they are annotated as candidates based on their substituted residue being identical to the substituted residue of functionally studied mutants and based on computational prediction of the pathogenicity of the mutation in COSMIC database:
ERBB2 L755M
ERBB2 L755W
ERBB2 D769N
ERBB2 V777E
ERBB2 V777M
ERBB2 T733I
ERBB2 T798I
ERBB2 V842E
ERBB2 L869Q
ERBB2 H878R
ERBB2 R896H
ERBB2 G776C
ERBB2 G776L
ERBB2 G776V
ERBB2 G778_P780insGSP
ERBB2 A771_Y772insYVMA

Literature References
PubMed ID Title Journal Year
18039657 Mutational activation of ErbB2 reveals a new protein kinase autoinhibition mechanism

Fan, YX, Wong, L, Ding, J, Spiridonov, NA, Johnson, RC, Johnson, GR

J. Biol. Chem. 2008
30314968 Combined Blockade of Activating ERBB2 Mutations and ER Results in Synthetic Lethality of ER+/HER2 Mutant Breast Cancer

Croessmann, S, Formisano, L, Kinch, LN, Gonzalez-Ericsson, PI, Sudhan, DR, Nagy, RJ, Mathew, A, Bernicker, EH, Cristofanilli, M, He, J, Cutler, RE, Lalani, AS, Miller, VA, Lanman, RB, Grishin, NV, Arteaga, CL

Clin. Cancer Res. 2019
16843263 HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors

Wang, SE, Narasanna, A, Perez-Torres, M, Xiang, B, Wu, FY, Yang, S, Carpenter, G, Gazdar, AF, Muthuswamy, SK, Arteaga, CL

Cancer Cell 2006
22046346 Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib

Kancha, RK, von Bubnoff, N, Bartosch, N, Peschel, C, Engh, RA, Duyster, J

PLoS ONE 2011
23843458 Carboxyl group footprinting mass spectrometry and molecular dynamics identify key interactions in the HER2-HER3 receptor tyrosine kinase interface

Collier, TS, Diraviyam, K, Monsey, J, Shen, W, Sept, D, Bose, R

J. Biol. Chem. 2013
30854046 Anti-tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations

Ogoshi, Y, Shien, K, Yoshioka, T, Torigoe, H, Sato, H, Sakaguchi, M, Tomida, S, Namba, K, Kurihara, E, Takahashi, Y, Suzawa, K, Yamamoto, H, Soh, J, Toyooka, S

Oncol Lett 2019
26545934 Antitumor effect of afatinib, as a human epidermal growth factor receptor 2-targeted therapy, in lung cancers harboring HER2 oncogene alterations

Suzawa, K, Toyooka, S, Sakaguchi, M, Morita, M, Yamamoto, H, Tomida, S, Ohtsuka, T, Watanabe, M, Hashida, S, Maki, Y, Soh, J, Asano, H, Tsukuda, K, Miyoshi, S

Cancer Sci. 2016
28274957 An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer

Hanker, AB, Brewer, MR, Sheehan, JH, Koch, JP, Sliwoski, GR, Nagy, R, Lanman, R, Berger, MF, Hyman, DM, Solit, DB, He, J, Miller, V, Cutler, RE, Lalani, AS, Cross, D, Lovly, CM, Meiler, J, Arteaga, CL

Cancer Discov 2017
23948973 Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2

Rexer, BN, Ghosh, R, Narasanna, A, Estrada, MV, Chakrabarty, A, Song, Y, Engelman, JA, Arteaga, CL

Clin. Cancer Res. 2013
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
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Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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