Regulation mechanisms of LIM-kinase-induced actin cytoskeletal reorganization

LIM激酶诱导肌动蛋白细胞骨架重组的调控机制

• 批准号: 11480213
• 负责人: MIZUNO Kensaku
• 金额: $ 3.65万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11480213/
• 关键词: LIM-kinase; LIMK; actin cytoskeleton; Rho; Rac; neurite outgrowth; TESK; コフィリン; インテグリン; LIMドメイン; プロテインキナーゼ; Rhoキナーゼ

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.

肌动蛋白细胞骨架重组在细胞运动、粘附、形态和胞质分裂中发挥重要作用。该项目的目的是阐明 LIM 激酶 (LIMK) 诱导肌动蛋白细胞骨架重组的调节机制。我们得到了以下结果： 1． LIMK的LIM结构域通过直接与蛋白激酶结构域相互作用，负向调节激酶活性。2． LIMK1 和 LIMK2 由 Rho 相关激酶通过 LIMK1 中的 Thr-508 和 LIMK2.3 中的 Thr-505 的磷酸化来激活。 TESK1在Ser-3位点磷酸化cofilin并诱导肌动蛋白重组，这些活性受到整合素介导的信号传导的调节。4．我们鉴定了一种果蝇LIM激酶，并发现它磷酸化cofilin并诱导肌动蛋白重组。5． LIMK-cofilin 信号通路在决定小脑颗粒神经元的轴突生长和信号蛋白 3A 诱导的背根神经节神经元的轴突塌陷中发挥作用。

项目成果

T.Amano, et al.: "LIM-kinase 2 induces formation of stress fibers, focal adhesions and membrane blebs, dependent on its activation by Rho-associated kinase."Biochem.J.. 354. 149-159 (2000)

T.Amano 等人：“LIM 激酶 2 依赖于 Rho 相关激酶的激活，诱导应力纤维、粘着斑和膜泡的形成。”Biochem.J. 354. 149-159 (2000)

M.Maekawa et al.: "Signaling from Rho to the actin cytoskeleton through protein kinases Rock and LIM-kinase"Science. 285巻. 895-898 (1999)

M. Maekawa 等人：“通过蛋白激酶 Rock 和 LIM 激酶从 Rho 向肌动蛋白细胞骨架发出信号”，科学 285. 895-898 (1999)。

K.Nagata et al.: "The N-terminal LIM domain negatively regulates the kinase activity of LIM-kinase 1"Biochem. J.. 343巻. 99-105 (1999)

K. Nagata 等人：“N 端 LIM 结构域负向调节 LIM 激酶 1 的激酶活性”Biochem J.. 343. 99-105 (1999)

Maekawa, M., et al.: "Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase."Science. 285. 895-898 (1999)

Maekawa, M. 等人：“通过蛋白激酶 ROCK 和 LIM 激酶从 Rho 向肌动蛋白细胞骨架发出信号。”科学。

Toshima, J., et al.: "Cofilin phosphorylation by protein kinase TESK1 and its role in integrin-mediated actin remodeling."Mol.Biol.Cell. (in press). (2001)

Toshima, J. 等人：“蛋白激酶 TESK1 导致的肌动蛋白丝切蛋白磷酸化及其在整合素介导的肌动蛋白重塑中的作用。”Mol.Biol.Cell。