Regulation mechanisms of LIM-kinase-induced actin cytoskeletal reorganization

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Actin cytoskeletal reorganization plays an important role in cell motility, adhesion, morphology, and cytokinesis. The aim of this project is to elucidate the regulation mechanisms of LIM-kinase (LIMK)-induced actin cytoskeletal reorganization. We have obtained following results.1. The LIM domains of LIMK negatively regulates the kinase activity by directly interacting with the protein kinase domain.2. LIMK1 and LIMK2 are activated by Rho-associated kinase, by phosphorylation of Thr-508 in LIMK1 and Thr-505 in LIMK2.3. TESK1 phosphorylates cofilin at Ser-3 and induces actin reorganization, and these activity are regulated by integrin-mediated signaling.4. We have identified a Drosophila LIM-kinase and found that it phosphorylates cofilin and induces actin reorganization.5. The LIMK-cofilin signaling pathway plays a role in determining axon outgrowth in cerebeller granule neurons and in semaphorin 3A-induced neurite collapse in dorsal root ganglion neurons.