p160 RhoA-binding kinase ROKα induces neurite retraction
p160 RhoA-binding kinase ROKα induces neurite retraction
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DOI：
10.1074/jbc.273.5.2489
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发表时间：
1998-01-30
影响因子：
4.8
通讯作者：
Negishi, M
中科院分区：
文献类型：
--
作者：
Katoh, H;Aoki, J;Negishi, M
我们先前报道了前列腺素E受体EP 3亚型的激活通过表达EP 3B受体的PC 12细胞中的小GTdR Rho引起神经突收缩（Katoh，H.，Negishi，M.，和Ichikawa，A.（1996）J.Biol.Chem.271，29780-29784）。然而，一个潜在的下游效应的Rho，诱导神经突起回缩没有确定，在这里，我们检查了形态的影响，p160 RhoA结合激酶ROK α，最近确定的RhoA的目标，对神经生长因子分化的PC 12细胞。ROK α的催化结构域的显微注射迅速诱导神经突收缩类似于由显微注射的组成型活性的Rho，Rho（V14），而激酶缺陷的ROK α的催化结构域的显微注射诱导的神经突收缩不诱导。即使预先注射了已知可抑制Rho的C3外切酶，也可观察到这种形态学变化。另一方面，显微注射ROK α的Rho结合结构域或普列克底物蛋白同源结构域抑制EP 3受体诱导的神经突收缩。这些结果表明，ROK α诱导神经突收缩作用于神经元细胞中Rho的下游。
We previously reported that the activation of prostaglandin E receptor EP3 subtype caused neurite retraction via small GTPase Rho in the EP3B receptor-expressing PC12 cells (Katoh, H., Negishi, M., and Ichikawa, A. (1996) J. Biol. Chem. 271, 29780-29784). However, a potential downstream effector of Rho that induces neurite retraction was not identified, Here we examined the morphological effect of p160 RhoA-binding kinase ROK alpha, a target for RhoA recently identified, on the nerve growth factor-differentiated PC12 cells. Microinjection of the catalytic domain of ROK alpha rapidly induced neurite retraction similar to that induced by microinjection of a constitutively active Rho, Rho(V14) whereas microinjection of the kinase-deficient catalytic domain of ROK alpha did not induce neurite retraction. This morphological change was observed even though C3 exoenzyme, which was known to inactivate Rho, had been preinjected. On the other hand, microinjection of the Rho-binding domain or the pleckstrin homology domain of ROK alpha inhibited the EP3 receptor-induced neurite retraction, These results demonstrate that ROK alpha induces neurite retraction acting downstream of Rho in neuronal cells.