p38 MAP kinase enhances EGF-induced apoptosis in A431 carcinoma cells by promoting tyrosine phosphorylation of STAT1

Biochem Biophys Res Commun. 2013 Jan 4;430(1):331-5. doi: 10.1016/j.bbrc.2012.11.041. Epub 2012 Nov 23.

Abstract

While epidermal growth factor (EGF) is a well known mitogen, high doses of EGF result in a paradoxical apoptotic response in the cells that overexpress EGF receptor such as A431 epidermoid carcinoma cells. EGF-induced apoptosis in A431 cells is dependent upon activation of transcription factor STAT1. In this study, we demonstrate that p38 MAP kinase is another important mediator of EGF-dependent pro-apoptotic response in A431 cells. By utilizing p38 MAP kinase inhibitors, SB203580 and BIRB0796, we significantly reduced the integral growth-inhibiting as well as pro-apoptotic effects of EGF. Moreover, we observed that inhibition of p38 MAP kinase markedly decreased phosphorylation of tyrosine 701 in STAT1, while neither EGF-induced accumulation nor serine phosphorylation of STAT1 was decreased. We propose that p38 MAP kinase mediates STAT1 tyrosine phosphorylation, thereby enforcing EGF-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Epidermal Growth Factor / pharmacology*
  • Humans
  • Phosphorylation / drug effects
  • STAT1 Transcription Factor / metabolism*
  • Tyrosine / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Tyrosine
  • Epidermal Growth Factor
  • p38 Mitogen-Activated Protein Kinases