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 journalArticle

Abstract

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
Volume8
Issue number11
DOIs
StatePublished - Nov 15 2013

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Phosphorylation
Epidermal Growth Factor Receptor
Tyrosine
Aptitude
Kinetic parameters
Detergents
Protein-Tyrosine Kinases
Ligation
Inhibition (Psychology)
Proteins
Chemical activation
Feedback
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Medicine(all)

Cite this

Wang, Z., Raines, L. L., Hooy, R. M., Roberson, H., Leahy, D. J., & Cole, P. A. (2013). Tyrosine phosphorylation of Mig6 reduces its inhibition of the epidermal growth factor receptor. ACS Chemical Biology, 8(11), 2373-2376. https://doi.org/10.1021/cb4005707

Tyrosine phosphorylation of Mig6 reduces its inhibition of the epidermal growth factor receptor. / Wang, Zhihong; Raines, Lily L.; Hooy, Richard M.; Roberson, Heather; Leahy, Daniel J.; Cole, Philip A.

In: ACS Chemical Biology, Vol. 8, No. 11, 15.11.2013, p. 2373-2376.

Research output: Contribution to journalArticle

Wang, Z, Raines, LL, Hooy, RM, Roberson, H, Leahy, DJ & Cole, PA 2013, 'Tyrosine phosphorylation of Mig6 reduces its inhibition of the epidermal growth factor receptor', ACS Chemical Biology, vol. 8, no. 11, pp. 2373-2376. https://doi.org/10.1021/cb4005707
Wang, Zhihong ; Raines, Lily L. ; Hooy, Richard M. ; Roberson, Heather ; Leahy, Daniel J. ; Cole, Philip A. / Tyrosine phosphorylation of Mig6 reduces its inhibition of the epidermal growth factor receptor. In: ACS Chemical Biology. 2013 ; Vol. 8, No. 11. pp. 2373-2376.
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