Hsp90 increases LIM kinase activity by promoting its homo-dimerization

Rong Li, Juliana Soosairajah, Daniel Harari, Ami Citri, John Price, Ling Ng Hooi, Craig J. Morton, Michael W. Parker, Yosef Yarden, Ora Bernard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageAmerican English
Pages (from-to)E417-E425
JournalFASEB Journal
Issue number8
StatePublished - Jun 2006
Externally publishedYes


  • Actin dynamics
  • Half-life
  • Rho-GTPases
  • Transphosphorylation


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