Stabilization of integrin-linked kinase by binding to Hsp90.
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.
Aoyagi
Yumiko
Y
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Fujita
Naoya
N
Tsuruo
Takashi
T
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D015536:Down-Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D018841:HSP90 Heat-Shock Proteins; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK