HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors.

doi:10.1016/j.ccr.2006.05.023

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HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors.

Cancer cell - 1 Jul 2006

Wang Shizhen Emily, Narasanna Archana, Perez-Torres Marianela, Xiang Bin, Wu Frederick Y, Yang Seungchan, Carpenter Graham, Gazdar Adi F, Muthuswamy Senthil K, Arteaga Carlos L

Abstract excerpt

HER2/Neu gene mutations have been identified in lung cancer. Expression of a HER2 mutant containing a G776(YVMA) insertion in exon 20 was more potent than wild-type HER2 in associating with and activating signal transducers, phosphorylating EGFR, and inducing survival, invasiveness, and tumorigenicity. HER2(YVMA) transphosphorylated kinase-dead EGFR(K721R) and EGFR(WT) in the presence of EGFR tyrosine kinase...

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HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors.

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