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Title: Stabilization of integrin-linked kinase by binding to Hsp90

Abstract

Integrin-linked kinase (ILK) is a serine/threonine kinase that interacts with the cytoplasmic domain of {beta}-integrins and growth factor receptors in response to extracellular signals. It is a key molecule in cell adhesion, proliferation, and cell survival. We found that treating cells with specific inhibitors of the heat shock protein 90 (Hsp90) caused rapid cell detachment. Screening the responsible proteins revealed a decreased amount of ILK in Hsp90 inhibitor-treated cells. ILK was identified as a new Hsp90 client protein because it formed a complex with Hsp90 and Cdc37, and binding was suppressed by Hsp90 inhibitors. Experiments with a series of ILK-deletion mutants revealed that the amino acid residues 377-406 were required for Hsp90 binding. Dissociation of ILK from Hsp90 shortened its half-life by promoting proteasome-dependent degradation. These results indicate that Hsp90 plays an important role in the stability of ILK in cells.

Authors:
 [1];  [2];  [1];
  1. Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)
  2. Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan)
Publication Date:
OSTI Identifier:
20710800
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 331; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2005.03.225; PII: S0006-291X(05)00727-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; GROWTH FACTORS; HALF-LIFE; HEAT-SHOCK PROTEINS; MUTANTS; NEOPLASMS; RECEPTORS; SERINE; THREONINE

Citation Formats

Aoyagi, Yumiko, Fujita, Naoya, Tsuruo, Takashi, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6, Ariake Kohtoh-ku, Tokyo 135-8550, and u-tokyo ac jp, E-mail: ttsuruo@iam. Stabilization of integrin-linked kinase by binding to Hsp90. United States: N. p., 2005. Web. doi:10.1016/j.bbrc.2005.03.225.
Aoyagi, Yumiko, Fujita, Naoya, Tsuruo, Takashi, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6, Ariake Kohtoh-ku, Tokyo 135-8550, & u-tokyo ac jp, E-mail: ttsuruo@iam. Stabilization of integrin-linked kinase by binding to Hsp90. United States. https://doi.org/10.1016/j.bbrc.2005.03.225
Aoyagi, Yumiko, Fujita, Naoya, Tsuruo, Takashi, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6, Ariake Kohtoh-ku, Tokyo 135-8550, and u-tokyo ac jp, E-mail: ttsuruo@iam. Fri . "Stabilization of integrin-linked kinase by binding to Hsp90". United States. https://doi.org/10.1016/j.bbrc.2005.03.225.
@article{osti_20710800,
title = {Stabilization of integrin-linked kinase by binding to Hsp90},
author = {Aoyagi, Yumiko and Fujita, Naoya and Tsuruo, Takashi and Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6, Ariake Kohtoh-ku, Tokyo 135-8550 and u-tokyo ac jp, E-mail: ttsuruo@iam},
abstractNote = {Integrin-linked kinase (ILK) is a serine/threonine kinase that interacts with the cytoplasmic domain of {beta}-integrins and growth factor receptors in response to extracellular signals. It is a key molecule in cell adhesion, proliferation, and cell survival. We found that treating cells with specific inhibitors of the heat shock protein 90 (Hsp90) caused rapid cell detachment. Screening the responsible proteins revealed a decreased amount of ILK in Hsp90 inhibitor-treated cells. ILK was identified as a new Hsp90 client protein because it formed a complex with Hsp90 and Cdc37, and binding was suppressed by Hsp90 inhibitors. Experiments with a series of ILK-deletion mutants revealed that the amino acid residues 377-406 were required for Hsp90 binding. Dissociation of ILK from Hsp90 shortened its half-life by promoting proteasome-dependent degradation. These results indicate that Hsp90 plays an important role in the stability of ILK in cells.},
doi = {10.1016/j.bbrc.2005.03.225},
url = {https://www.osti.gov/biblio/20710800}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 331,
place = {United States},
year = {2005},
month = {6}
}