Regulation of ROCK Activity in Cancer

Marie Morgan-Fisher, Ulla M Wewer, Atsuko Yoneda

Research output: Contribution to journalJournal articleResearchpeer-review

100 Citations (Scopus)

Abstract

Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)-loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.
Original languageEnglish
JournalJournal of Histochemistry and Cytochemistry
Volume61
Issue number3
Pages (from-to)185-198
ISSN0022-1554
DOIs
Publication statusPublished - 29 Jan 2013

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