Hsp90 increases LIM kinase activity by promoting its homo-dimerization

Full text for this resource is not available from the Research Repository.

Li, Rong, Soosairajah, Juliana, Harari, Daniel, Citri, Ami, Price, John, Ng, Hooi Ling, Morton, Craig J, Parker, Michael W, Yarden, Yosef and Bernard, Ora (2006) Hsp90 increases LIM kinase activity by promoting its homo-dimerization. FASEB Journal, 20 (8). pp. 1218-1220. ISSN 0892-6638 (print) 1530-6860 (online)


LIM kinase 1 (LIMK1) is a serine protein kinase that regulates the actin cytoskeleton by phosphorylation and inactivation of actin depolymerizing factor cofilin. LIMK1 activity is regulated by the Rho-GTPases via their serine/threonine kinase effectors Rho-kinase and p21-activated kinases 1 and 4 that phosphorylate LIMK1 on threonine 508 in its activation loop. The purpose of this study was to elucidate the pathway leading to the stability of LIMK1, a protein with a half-life of ∼20 h. Because the half-life of kinase-dead LIMK1 is only 4 h, it is suggestive that trans- or auto-phosphorylation is responsible for the stabilization of LIMK1. Using known Hsp90 inhibitors, we have shown that the half-life of LIMK1 in cells depends on the presence of active Hsp90. Furthermore, endogenous LIMK1 coimmunoprecipitated with endogenous Hsp90 and this interaction promoted LIMK1 homodimer formation as seen by cross-linking experiments. Hsp90 binds LIMK1 via a recognition sequence within the LIMK1 kinase domain, homologous to that of ErbB-2. Mutation of a proline residue within this sequence to glutamic acid reduces its interaction with Hsp90, inhibits homodimer formation, and reduces its half-life to 4 h. These findings implicate Hsp90 in the stabilization of LIMK1 by promoting homodimer formation and transphosphorylation. Li, R., Soosairajah, J., Harari, D., Citri, A., Price, J., Ng, H. L., Morton, C. J., Parker, M. W., Yarden, Y., Bernard, O. Hsp90 increases LIM kinase activity by promoting its homo-dimerization.

Dimensions Badge

Altmetric Badge

Item type Article
URI https://vuir.vu.edu.au/id/eprint/22434
DOI https://doi.org/10.1096/fj.05-5258fje
Official URL http://www.fasebj.org/content/20/8/1218
Subjects Historical > FOR Classification > 0304 Medicinal and Bimolecular Chemistry
Current > Division/Research > College of Health and Biomedicine
Keywords Rho-GTPases, actin dynamics, half-life, transphosphorylation
Citations in Scopus 38 - View on Scopus
Download/View statistics View download statistics for this item

Search Google Scholar

Repository staff login