The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

Unbekandt, M. and Olson, M. F. (2014) The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer. Journal of Molecular Medicine, 92(3), pp. 217-225. (doi: 10.1007/s00109-014-1133-6)

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Publisher's URL: http://dx.doi.org/10.1007/s00109-014-1133-6

Abstract

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Unbekandt, Dr Mathieu and Olson, Professor Michael
Authors: Unbekandt, M., and Olson, M. F.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Journal of Molecular Medicine
Publisher:Springer Verlag
ISSN:0946-2716
ISSN (Online):1432-1440
Published Online:20 February 2014
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Journal of Molecular Medicine 92(3):217-225
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
576111Development of a novel drug targeting MRCK and ROCKII for the treatment of invasive and/or metastatic cancerMichael OlsonMedical Research Council (MRC)MR/J005126/1ICS - BEATSON INSTITUTE FOR CANCER RES.