Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Laura Geffert
  • Jong YunEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101741


Historical Background

MRCK stands for Myotonic dystrophy-Related Cdc42-binding Kinase. The protein earned this name because it binds to Cdc42 with a significant homology to the DMPK (Dystrophia Myotonica Protein Kinase) kinase domain. Prior to the identification of MRCK, many of the RHO-family GTPase effectors homologous to MRCK were discovered. After the identification of the RHO-family GTPases, Rho, Rac1, and Cdc42 (Manser et al. 1994), each of which plays distinctive roles in cytoskeletal reorganization associated with growth and differentiation, the search began for the interacting proteins and potential targets of the p21 (Cdc42/Rac) Rho family that might convey signals downstream...

This is a preview of subscription content, log in to check access.


  1. Bishop A, Hall A. Rho GTPases and their effector proteins. Biochem J. 2000;348:241–55.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Choi S, Czifra G, Kedei N, Lewin N, Lazar J, Pu Y, Marquez V, Blumberg P. Characterization of the interaction of phorbol esters with the C1 domain of MRCK alpha/beta. J Biol Chem. 2008;283:10543–9.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Heikkila T, Wheatley E, Crighton D, Schroder E, Boakes A, Kaye S, Mezna M, Pang L, Rushbrooke M, Turnbull A. Co-crystal structures of inhibitors with MRCKβeta, a key regulator of tumor cell invasion. PLoS One. 2011;6:e24825.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Huo L, Wen W, Wang R, Kam C, Xia J, Feng W, Zhang M. Cdc42-dependent formation of the ZO-1/MRCKβ complex at the leading edge controls cell migration. EMBO. 2011;30:665–78.CrossRefGoogle Scholar
  5. Kale V, Hengst J, Desai D, Dick T, Choe K, Colledge A, Takahashi Y, Sung S, Amin S, Yun J. A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion. Cancer Lett. 2014;354:299–310.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Leung T, Chen X-QQ, Manser E, Lim L. The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Mol Cell Biol. 1996;16(10):5313–27.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Leung T, Chen X-QQ, Tan I, Manser E, Lim L. Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization. Mol Cell Biol. 1998;18:130–40.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Lowe H, Watson C, Badal S, Toyang N, Bryant J. Cycloartane3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro. Cancer Cell Int. 2012;12:46.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature. 1994;367(6458):40–6.CrossRefPubMedGoogle Scholar
  10. Moncrieff C, Bailey M, Morrison N, Johnson K. Cloning and chromosomal localization of human Cdc42-binding protein kinase beta. Genomics. 1999;57:297–300.CrossRefPubMedGoogle Scholar
  11. Ng Y, Tan I, Lim L, Leung T. Expression of the human myotonic dystrophy kinase-related Cdc42-binding kinase g is regulated by promoter DNA methylation and Sp1 binding. J Biol Chem. 2004;279(33):34156–66.CrossRefPubMedGoogle Scholar
  12. Tan I, Seow K, Lim L, Leung T. Intermolecular and intramolecular interactions regulate catalytic activity of myotonic dystrophy kinase-related Cdc42-binding kinase alpha. Mol Cell Biol. 2001;21(8):2767–78.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Tan I, Cheong A, Lim L, Leung T. Genomic organization of human myotonic dystrophy kinase-related Cdc42-binding kinase a reveals multiple alternative splicing and functional diversity. Gene. 2003;304:107–15.CrossRefPubMedGoogle Scholar
  14. Unbekandt M, Croft D, Crighton D, Mezna M, McArthur D, McConnell P, Schuttelkopf A, Belshaw S, Pannifer A, Sime M, Bower J, Drysdale M, Olson M. A novel small-molecule MRCK inhibitor blocks cancer cell invasion. Cell Comm Signal. 2014;12:54.CrossRefGoogle Scholar
  15. Wilkinson S, Paterson H, Marshall C. Cdc42-MRCK and Rho-ROCK signalling cooperate in myosin phosphorylation and cell invasion. Nat Cell Biol. 2005;7(3):255–61.CrossRefPubMedGoogle Scholar
  16. Zhao Y, Loyer P, Li H, Valentine V, Kidd V, Kraft A. Cloning and chromosomal location of a novel member of the myotonic dystrophy family of protein kinases. JBC. 1997;15(11):10013–20.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Penn State University College of MedicineHersheyUSA