HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/1/G135    most recent 00139.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Mammen, J. M. V. Articles by Matthews, J. B. Search for Related Content PubMed PubMed Citation Articles by Mammen, J. M. V. Articles by Matthews, J. B.

MUCOSAL BIOLOGY

Differential subcellular targeting of PKC- in response to pharmacological or ischemic stimuli in intestinal epithelia

Epithelial Pathobiology Research Group, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio

Submitted 31 March 2004 ; accepted in final form 25 August 2004

Ischemia is the central pathogenic factor underlying a spectrum of intestinal disorders. The study of the cellular signaling responses to ischemic stress in nonepithelial cells has progressed substantially in the previous several years, but little is known about the response in epithelial cells. Unique features of the epithelial response to ischemic stress suggest differential regulation with regards to signaling. The PKC family of proteins has been implicated in ischemic stress in nonepithelial systems. The role of PKC isoforms in chemical ischemia in intestinal epithelial cells is evaluated in this study. Additionally, the phosphorylation of the F-actin cross-linking protein myristoylated alanine-rich C kinase substrate (MARCKS) is also studied. Chemical ischemia resulted in the transient activation of only the isoform PKC- as detected by translocation employing the subcellular fractionation technique. The pharmacological agonists phorbol 12-myristate 13-acetate and carbachol also led to the translocation of PKC-. By immunofluoresence, MARCKS is noted to be located at the lateral membrane under control conditions. In response to carbachol, MARCKS translocates to the cytosol, indicating its phosphorylation, which is additionally confirmed biochemically. Consistent with this observation, carbachol induces the translocation of PKC- to proximity with MARCKS at the lateral membrane. In response to chemical ischemia, MARCKS fails to translocate and phosphorylation does not increase. Additionally, the translocation of PKC- is not to the lateral membrane but rather basally. The data suggest that the differential translocation of PKC- in response to pharmacological agonists versus ischemic stress may lead to different effects on downstream targets.

F-actin; hypoxia; ischemia; myristolated alanine-rich C kinase substrate; phorbol ester

This article has been cited by other articles:

				J. C. Ibla, J. Khoury, T. Kong, A. Robinson, and S. P. Colgan Transcriptional repression of Na-K-2Cl cotransporter NKCC1 by hypoxia-inducible factor-1 Am J Physiol Cell Physiol, August 1, 2006; 291(2): C282 - C289. [Abstract] [Full Text] [PDF]