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p160 RhoA-binding Kinase ROKα Induces Neurite Retraction

1998; Elsevier BV; Volume: 273; Issue: 5 Linguagem: Inglês

10.1074/jbc.273.5.2489

1083-351X

Hironori Katoh, Junko Aoki, Atsushi Ichikawa, Masahiko Negishi,

Receptor Mechanisms and Signaling

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 ROKα, a target for RhoA recently identified, on the nerve growth factor-differentiated PC12 cells. Microinjection of the catalytic domain of ROKα 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 ROKα 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 ROKα inhibited the EP3 receptor-induced neurite retraction. These results demonstrate that ROKα induces neurite retraction acting downstream of Rho in neuronal cells.