University of Birmingham Distinct Roles for ROCK1 and ROCK2 in the Regulation of Keratinocyte Differentiation

Background: The human epidermis is comprised of several layers of specialized epithelial cells called keratinocytes. Normal homoeostasis of the epidermis requires that the balance between keratinocyte proliferation and terminal differentiation be tightly regulated. The mammalian serine/threonine kinases (ROCK1 and ROCK2) are well-characterised downstream effectors of the small GTPase RhoA. We have previously demonstrated that the RhoA/ROCK signalling pathway plays an important role in regulation of human keratinocyte proliferation and terminal differentiation. In this paper we addressed the question of which ROCK isoform was involved in regulation of keratinocyte differentiation. Methodology and Principal Findings: We used RNAi to specifically knockdown ROCK1 or ROCK2 expression in cultured human keratinocytes. ROCK1 depletion results in decreased keratinocyte adhesion to fibronectin and an increase in terminal differentiation. Conversely, ROCK2 depletion results in increased keratinocyte adhesion to fibronectin and inhibits terminal differentiation. Conclusion: These data suggest that ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation. Citation: Lock FE, Hotchin NA (2009) Distinct Roles for ROCK1 and ROCK2 in the Regulation of Keratinocyte Differentiation. PLoS ONE 4(12): e8190. doi:10.1371/ journal.pone.0008190 Editor: Joy Sturtevant, Louisiana State University, United States of America Received September 29, 2009; Accepted November 13, 2009; Published December 4, 2009 Copyright: ! 2009 Lock, Hotchin. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by a Cancer Research UK project grant (C20692). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: NAH is an academic editor for PLoS ONE. * E-mail: [email protected]