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

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 PTP{alpha}, 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.

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [1];  [3];  [1]
  1. Department of Radiation Research, Faculty of Medicine, University of Tokyo, Tokyo 113-0033 (Japan)
  2. Department of Radiation Research, Faculty of Medicine, University of Tokyo, Tokyo 113-0033 (Japan). E-mail: hosoi@m.u-tokyo.ac.jp
  3. Department of Radiology, Faculty of Medicine, University of Tokyo, Tokyo 113-0033 (Japan)
Publication Date:
OSTI Identifier:
20798828
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 341; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2005.12.193; PII: S0006-291X(06)00019-2; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; BIOLOGICAL RADIATION EFFECTS; GROWTH FACTORS; IONIZING RADIATIONS; IRRADIATION; LIGANDS; PHOSPHORYLATION; RECEPTORS; TYROSINE

Citation Formats

Li Zhiping, Hosoi, Yoshio, Cai Keshong, Tanno, Yuji, Matsumoto, Yoshihisa, Enomoto, Atsushi, Morita, Akinori, Nakagawa, Keiichi, and Miyagawa, Kiyoshi. Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal growth factor receptor transactivation by X-irradiation. United States: N. p., 2006. Web.
Li Zhiping, Hosoi, Yoshio, Cai Keshong, Tanno, Yuji, Matsumoto, Yoshihisa, Enomoto, Atsushi, Morita, Akinori, Nakagawa, Keiichi, & Miyagawa, Kiyoshi. Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal growth factor receptor transactivation by X-irradiation. United States.
Li Zhiping, Hosoi, Yoshio, Cai Keshong, Tanno, Yuji, Matsumoto, Yoshihisa, Enomoto, Atsushi, Morita, Akinori, Nakagawa, Keiichi, and Miyagawa, Kiyoshi. Fri . "Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal growth factor receptor transactivation by X-irradiation". United States. doi:.
@article{osti_20798828,
title = {Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal growth factor receptor transactivation by X-irradiation},
author = {Li Zhiping and Hosoi, Yoshio and Cai Keshong and Tanno, Yuji and Matsumoto, Yoshihisa and Enomoto, Atsushi and Morita, Akinori and Nakagawa, Keiichi and Miyagawa, Kiyoshi},
abstractNote = {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 PTP{alpha}, 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.},
doi = {},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 341,
place = {United States},
year = {Fri Mar 10 00:00:00 EST 2006},
month = {Fri Mar 10 00:00:00 EST 2006}
}