Birkenfeld J, Betz H, Roth D
Department of Neurochemistry, Max-Planck-Institute for Brain Research, Frankfurt, Germany.
J Neurochem. 2001 Aug;78(4):924-7. doi: 10.1046/j.1471-4159.2001.00500.x.
Lin-11, Isl-1 and Mec-3 (LIM) kinases are serine/threonine kinases that phosphorylate cofilin, an actin depolymerizing protein. LIM kinases have a highly modular structure composed of two N-terminal LIM domains (LIM 1/2), a PSD-95, Dlg and ZO-1 (PDZ) domain and a C-terminal protein kinase domain. Here, we overexpressed individual domains of mouse LIM kinase 1 (LIMK1) in PC12 cells and investigated their effects on neurite outgrowth. Although none of the LIMK1 domains had an effect on spontaneous neurite outgrowth, the N-terminal LIM 1/2 domains strongly inhibited differentiation of PC12 cells after stimulation with both nerve growth factor (NGF) and the Rho-kinase inhibitor Y-27632. In contrast, the overexpressed PDZ domain reduced neurite outgrowth only when differentiation had been induced by Y-27632, but not by NGF. Our data suggest that the different non-catalytic N-terminal domains of LIMK1 contribute to the regulation of neurite extension by using distinct signal transduction pathways.
Lin-11、Isl-1和Mec-3（LIM）激酶是丝氨酸/苏氨酸激酶，可磷酸化肌动蛋白解聚蛋白丝切蛋白。LIM激酶具有高度模块化的结构，由两个N端LIM结构域（LIM 1/2）、一个突触后密度蛋白95（PSD-95）、盘状大蛋白（Dlg）和紧密连接蛋白1（ZO-1）（PDZ）结构域以及一个C端蛋白激酶结构域组成。在此，我们在PC12细胞中过表达小鼠LIM激酶1（LIMK1）的各个结构域，并研究它们对神经突生长的影响。尽管LIMK1的任何结构域对自发神经突生长均无影响，但N端LIM 1/2结构域在神经生长因子（NGF）和Rho激酶抑制剂Y-27632刺激后强烈抑制PC12细胞的分化。相比之下，过表达的PDZ结构域仅在Y-27632诱导分化时才减少神经突生长，而在NGF诱导分化时则不然。我们的数据表明，LIMK1不同的非催化性N端结构域通过使用不同的信号转导途径参与神经突延伸的调节。
