Lim kinases, regulators of actin dynamics

Abstract

The members of the LIM kinase (LIMK) family, which include LIMK 1 and 2, are serine protein kinases involved in the regulation of actin polymerisation and microtubule disassembly. Their activity is regulated by phosphorylation of a threonine residue within the activation loop of the kinase by p21-activated kinases 1 and 4 and by Rho kinase. LIMKs phosphorylate and inactivate the actin depolymerising factors ADF/cofilin resulting in net increase in the cellular filamentous actin. Hsp90 regulates the levels of the LIM kinase proteins by promoting their homo-dimerisation and trans-phosphorylation. Rnf6 is an E3 ubiquitin ligase responsible for LIMK degradation in neurons. The activity of LIMK1 is also required for microtubule disassembly in endothelial cells. While LIMK1 localizes mainly at focal adhesions, LIMK2 is found in cytoplasmic punctae, suggesting that they may have different cellular functions. LIMK1 was shown to be involved in cancer metastasis, while LIMK2 activation promotes cells cycle progression.