Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion.

Abstract:

:Actomyosin contractility is a mechanism by which cells exert locomotory force against their environment. Signalling downstream of the small GTPase Rho increases contractility through Rho-kinase (ROCK)-mediated regulation of myosin-II light chain (MLC2) phosphorylation. Cdc42 signalling has been shown to control cell polarity. Tumour cells can move through a three-dimensional matrix with either a rounded morphology characterized by Rho-ROCK dependence or with an elongated morphology characterized by Rho-ROCK independence. Here we show that contractility necessary for elongated morphology and invasion can be generated by Cdc42-MRCK signalling. MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) cooperates with ROCK in the maintenance of elongated morphology and invasion and either MRCK or ROCK is sufficient for MLC2 phosphorylation, through the inhibitory phosphorylation of myosin phosphatase. By contrast, in rounded ROCK-dependent movement, where MLC2 phosphorylation is higher, MRCK has a smaller role. Our data show that a Cdc42-MRCK signal mediates myosin-dependent cell motility and highlight convergence between Rho and Cdc42 signalling.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Wilkinson S,Paterson HF,Marshall CJ

doi

10.1038/ncb1230

keywords:

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

255-61

issue

3

eissn

1465-7392

issn

1476-4679

pii

ncb1230

journal_volume

7

pub_type

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