Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

GCK-3, a Newly Identified Ste20 Kinase, Binds To and Regulates the Activity of a Cell Cycle–dependent ClC Anion Channel

GCK-3, a Newly Identified Ste20 Kinase, Binds To and Regulates the Activity of a Cell... CLH-3b is a Caenorhabditis elegans ClC anion channel that is expressed in the worm oocyte. The channel is activated during oocyte meiotic maturation and in response to cell swelling by serine/threonine dephosphorylation events mediated by the type 1 phosphatases GLC-7α and GLC-7β. We have now identified a new member of the Ste20 kinase superfamily, GCK-3, that interacts with the CLH-3b COOH terminus via a specific binding motif. GCK-3 inhibits CLH-3b in a phosphorylation-dependent manner when the two proteins are coexpressed in HEK293 cells. clh-3 and gck-3 are expressed predominantly in the C. elegans oocyte and the fluid-secreting excretory cell. Knockdown of gck-3 expression constitutively activates CLH-3b in nonmaturing worm oocytes. We conclude that GCK-3 functions in cell cycle– and cell volume–regulated signaling pathways that control CLH-3b activity. GCK-3 inactivates CLH-3b by phosphorylating the channel and/or associated regulatory proteins. Our studies provide new insight into physiologically relevant signaling pathways that control ClC channel activity and suggest novel mechanisms for coupling cell volume changes to cell cycle events and for coordinately regulating ion channels and transporters that control cellular Cl − content, cell volume, and epithelial fluid secretion. C. elegans meiotic maturation phosphorylation oocyte cell volume Footnotes Abbreviations used in this paper: CHO, Chinese hamster ovary; dsRNA, double strand RNA; GCK, germinal center kinase; GST, glutathione S-transferase; HEK, human embryonic kidney; PAK, p21-activated kinase. Submitted: 12 November 2004 Accepted: 6 January 2005 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of General Physiology Rockefeller University Press

GCK-3, a Newly Identified Ste20 Kinase, Binds To and Regulates the Activity of a Cell Cycle–dependent ClC Anion Channel

Download PDF
13 pages

Loading next page...
 
/lp/rockefeller-university-press/gck-3-a-newly-identified-ste20-kinase-binds-to-and-regulates-the-GUHYsbp0FY

References (63)

Publisher
Rockefeller University Press
Copyright
Copyright © 2005, by The Rockefeller University Press
ISSN
0022-1295
eISSN
1540-7748
DOI
10.1085/jgp.200409215
pmid
15684092
Publisher site
See Article on Publisher Site

Abstract

CLH-3b is a Caenorhabditis elegans ClC anion channel that is expressed in the worm oocyte. The channel is activated during oocyte meiotic maturation and in response to cell swelling by serine/threonine dephosphorylation events mediated by the type 1 phosphatases GLC-7α and GLC-7β. We have now identified a new member of the Ste20 kinase superfamily, GCK-3, that interacts with the CLH-3b COOH terminus via a specific binding motif. GCK-3 inhibits CLH-3b in a phosphorylation-dependent manner when the two proteins are coexpressed in HEK293 cells. clh-3 and gck-3 are expressed predominantly in the C. elegans oocyte and the fluid-secreting excretory cell. Knockdown of gck-3 expression constitutively activates CLH-3b in nonmaturing worm oocytes. We conclude that GCK-3 functions in cell cycle– and cell volume–regulated signaling pathways that control CLH-3b activity. GCK-3 inactivates CLH-3b by phosphorylating the channel and/or associated regulatory proteins. Our studies provide new insight into physiologically relevant signaling pathways that control ClC channel activity and suggest novel mechanisms for coupling cell volume changes to cell cycle events and for coordinately regulating ion channels and transporters that control cellular Cl − content, cell volume, and epithelial fluid secretion. C. elegans meiotic maturation phosphorylation oocyte cell volume Footnotes Abbreviations used in this paper: CHO, Chinese hamster ovary; dsRNA, double strand RNA; GCK, germinal center kinase; GST, glutathione S-transferase; HEK, human embryonic kidney; PAK, p21-activated kinase. Submitted: 12 November 2004 Accepted: 6 January 2005

Journal

The Journal of General Physiology – Rockefeller University Press

Published: Feb 1, 2005

There are no references for this article.