Tyrosine phosphorylation of Mig6 reduces its inhibition of the epidermal growth factor receptor

Zhihong Wang, Lily L. Raines, Richard M. Hooy, Heather Roberson, Daniel J. Leahy, Philip A. Cole

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Under physiological conditions, epidermal growth factor receptor (EGFR) tyrosine kinase activity is tightly controlled through the coordinated action of both positive and negative regulators. Aberrant EGFR activation occurs frequently in many cancer types, and the endogenous EGFR feedback inhibitor, Mig6/RALT, is more efficiently phosphorylated by oncogenic EGFR variants. We have utilized expressed protein ligation to generate semisynthetic Tyr394 phosphorylated and unphosphorylated forms of the Mig6 protein and shown that phosphorylation of Mig6 reduces its ability to inhibit purified, near full-length EGFR (tEGFR). We also demonstrate that the kinetic parameters of tEGFR are similar whether solubilized in detergent or reconstitutued in nanodisc bilayers. These findings suggest a mechanism by which EGFR and its family members evade negative regulation by Mig6 under pathological conditions.

Original languageEnglish (US)
Pages (from-to)2373-2376
Number of pages4
JournalACS Chemical Biology
Issue number11
StatePublished - Nov 15 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine


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