AJP - GI Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 278: G765-G774, 2000;
0193-1857/00 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (15)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Umar, S.
Right arrow Articles by Morris, A. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Umar, S.
Right arrow Articles by Morris, A. P.
Vol. 278, Issue 5, G765-G774, May 2000

Murine colonic mucosa hyperproliferation. II. PKC-beta activation and cPKC-mediated cellular CFTR overexpression

Shahid Umar, Joseph H. Sellin, and Andrew P. Morris

Department of Integrative Biology, Pharmacology, and Physiology; and Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, The University of Texas Health Science Center at Houston, Medical School, Houston, Texas 77030

In the companion article (Umar S, Scott J, Sellin JH, Dubinsky WP, and Morris AP, Am J Physiol Gastrointest Liver Physiol 278: 753-764, 2000), we have shown that transmissible murine colonic hyperplasia (TMCH) increased cellular cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein expression, relocalized CFTR within colonocytes, and enhanced mucosal cAMP-dependent Cl- secretion. We show here that these changes were dependent on elevated cellular levels of membrane-bound Ca2+- and diacylglycerol-sensitive protein kinase C (PKC) activity (12-fold), induced by selective (3- to 4-fold) rises in conventional PKC (cPKC) isoform expression and membrane translocation. Three cPKC isoforms were detected in isolated crypts: alpha , beta 1, and beta 2. cPKC-beta 1 rises preceded and those of cPKC-alpha and cPKC-beta 2 paralleled cellular hyperproliferation and its effects on CFTR expression and cAMP-dependent Cl- current secretion. Only cPKC-beta 1 and cPKC-beta 2 were membrane translocated during TMCH. Furthermore, only cPKC-beta 1 trafficked to the nucleus, whereas cPKC-beta 2 remained partitioned among cytosolic, membrane, and cytoskeletal subcellular fractions. Modest increases in novel PKC-epsilon (nPKC-epsilon ) expression and subcellular membrane partitioning were recorded during TMCH, but no changes were seen for PKC-delta or -eta . No nPKC isoform nuclear partitioning was detected. The orally bioactive cPKC inhibitor Ro-32-0432 reversed both TMCH and elevated cellular CFTR mRNA levels, whereas a pharmacologically inert analog (Ro-31-6045) failed to inhibit either response. On the basis of these facts, we present a new hypothesis whereby PKC-dependent cellular proliferation promotes endogenous cellular CFTR levels. PKC-beta 1 was identified as a candidate regulatory PKC isoform.

protein kinase C; cystic fibrosis transmembrane conductance regulator; anion transport; regulation; mouse


This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. Q. van der Merwe, F. Moreau, and W. K. MacNaughton
Protease-activated receptor-2 stimulates intestinal epithelial chloride transport through activation of PLC and selective PKC isoforms
Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1258 - G1266.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Umar, Y. Wang, A. P. Morris, and J. H. Sellin
Dual alterations in casein kinase I-{epsilon} and GSK-3beta modulate beta-catenin stability in hyperproliferating colonic epithelia
Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G599 - G607.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. R. Broughman, L. Sun, S. Umar, J. Scott, J. H. Sellin, and A. P. Morris
Chronic PKC-beta activation in HT-29 Cl.19a colonocytes prevents cAMP-mediated ion secretion by inhibiting apical membrane current generation
Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G318 - G330.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. R. Broughman, L. Sun, S. Umar, J. H. Sellin, and A. P. Morris
Chronic PKC-beta2 activation in HT-29 Cl.19a colonocytes prevents cAMP-mediated ion secretion by inhibiting apical membrane CFTR targeting
Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G331 - G344.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
V Chappe, D A Hinkson, T Zhu, X-B Chang, J R Riordan, and J W Hanrahan
Phosphorylation of protein kinase C sites in NBD1 and the R domain control CFTR channel activation by PKA
J. Physiol., April 1, 2003; 548(1): 39 - 52.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. H. Sellin, S. Umar, J. Xiao, and A. P. Morris
Increased {beta}-Catenin Expression and Nuclear Translocation Accompany Cellular Hyperproliferation in Vivo
Cancer Res., April 1, 2001; 61(7): 2899 - 2906.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Umar, J. H. Sellin, and A. P. Morris
Increased nuclear translocation of catalytically active PKC-zeta during mouse colonocyte hyperproliferation
Am J Physiol Gastrointest Liver Physiol, July 1, 2000; 279(1): G223 - G237.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online