Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion - PubMed (original) (raw)
doi: 10.1038/ncb1230. Epub 2005 Feb 20.
Affiliations
- PMID: 15723050
- DOI: 10.1038/ncb1230
Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion
Simon Wilkinson et al. Nat Cell Biol. 2005 Mar.
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.
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