Review
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 28, 2008; 14(40): 6115-6121
Published online Oct 28, 2008. doi: 10.3748/wjg.14.6115
Ste20-related proline/alanine-rich kinase: A novel regulator of intestinal inflammation
Yutao Yan, Didier Merlin
Yutao Yan, Didier Merlin, Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, United States
Author contributions: Yan Y and Merlin D contributed equally to this work.
Correspondence to: Didier Merlin, PhD, Associate Professor, Emory University Department of Medicine Division of Digestive Diseases 615 Michael Street Atlanta GA 30322, United States. dmerlin@emory.edu
Telephone: +01-404-7276454 Fax: +01-404-727-5767
Received: May 14, 2008
Revised: July 28, 2008
Accepted: August 3, 2008
Published online: October 28, 2008
Abstract

Recently, inflammatory bowel disease (IBD) has been the subject of considerable research, with increasing attention being paid to the loss of intestinal epithelial cell barrier function as a mechanism of pathogenesis. Ste20-related proline/alanine-rich kinase (SPAK) is involved in regulating barrier function. SPAK is known to interact with inflammation-related kinases (such as p38, JNK, NKCC1, PKCtheta;, WNK and MLCK), and with transcription factor AP-1, resulting in diverse biological phenomena, including cell differentiation, cell transformation and proliferation, cytoskeleton rearrangement, and regulation of chloride transport. This review examines the involvement of Ste20-like kinases and downstream mitogen-activated protein kinases (MAPKs) pathways in the pathogenesis and control of intestinal inflammation. The primary focus will be on the molecular features of intestinal inflammation, with an emphasis on the interaction between SPAK and other molecules, and the effect of these interactions on homeostatic maintenance, cell volume regulation and increased cell permeability in intestinal inflammation.

Keywords: Inflammatory bowel diseases; WNK; NKCC1; Barrier function; Ste20-related proline/alanine-rich kinase