Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal growth factor receptor transactivation by X-irradiation

Zhiping Li, Yoshio Hosoi, Keshong Cai, Yuji Tanno, Yoshihisa Matsumoto, Atsushi Enomoto, Akinori Morita, Keiichi Nakagawa, Kiyoshi Miyagawa

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Exposure of MDA-MB-468 cells to ionizing radiation (IR) caused biphasic activation of ERK as indicated by its phosphorylation at Thr202/Tyr204. Specific epidermal growth factor receptor (EGFR) inhibitor AG1478 and specific Src inhibitor PP2 inhibited IR-induced ERK1/2 activation but phosphatidylinositol-3 kinase inhibitor wortmannin did not. IR caused EGFR tyrosine phosphorylation, whereas it did not induce EGFR autophosphorylation at Tyr992, Tyr1045, and Tyr1068 or Src-dependent EGFR phosphorylation at Tyr845. SHP-2, which positively regulates EGFR/Ras/ERK signaling cascade, became activated by IR as indicated by its phosphorylation at Tyr542. This activation was inhibited by PP2 not by AG1478, which suggests Src-dependent activation of SHP-2. Src and PTPα, which positively regulates Src, became activated as indicated by phosphorylation at Tyr416 and Tyr789, respectively. These data suggest that IR-induced ERK1/2 activation involves EGFR through a Src-dependent pathway that is distinct from EGFR ligand activation.

Original languageEnglish
Pages (from-to)363-368
Number of pages6
JournalBiochemical and biophysical research communications
Volume341
Issue number2
DOIs
Publication statusPublished - 2006 Mar 10
Externally publishedYes

Keywords

  • AG1478
  • EGFR
  • ERK
  • Ionizing radiation
  • PP2
  • SHP-2
  • Src
  • Transactivation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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