Protein Kinase C Signaling Mediates a Program of Cell Cycle Withdrawal in the Intestinal Epithelium Export

@article{citeulike:2919903, abstract = {Members of the protein kinase C (PKC) family of signal transduction molecules have been widely implicated in regulation of cell growth and differentiation, although the underlying molecular mechanisms involved remain poorly defined. Using combined in vitro and in vivo intestinal epithelial model systems, we demonstrate that PKC signaling can trigger a coordinated program of molecular events leading to cell cycle withdrawal into G0. PKC activation in the IEC-18 intestinal crypt cell line resulted in rapid downregulation of D-type cyclins and differential induction of p21waf1/cip1 and p27kip1, thus targeting all of the major G1/S cyclin-dependent kinase complexes. These events were associated with coordinated alterations in expression and phosphorylation of the pocket proteins p107, pRb, and p130 that drive cells to exit the cell cycle into G0 as indicated by concomitant downregulation of the DNA licensing factor cdc6. Manipulation of PKC isozyme levels in IEC-18 cells demonstrated that PKC{alpha} alone can trigger hallmark events of cell cycle withdrawal in intestinal epithelial cells. Notably, analysis of the developmental control of cell cycle regulatory molecules along the crypt-villus axis revealed that PKC{alpha} activation is appropriately positioned within intestinal crypts to trigger this program of cell cycle exit-specific events in situ. Together, these data point to PKC{alpha} as a key regulator of cell cycle withdrawal in the intestinal epithelium. 10.1083/jcb.151.4.763}, author = {Frey, Mark R. and Clark, Jennifer A. and Leontieva, Olga and Uronis, Joshua M. and Black, Adrian R. and Black, Jennifer D.}, citeulike-article-id = {2919903}, citeulike-linkout-0 = {http://dx.doi.org/10.1083/jcb.151.4.763}, citeulike-linkout-1 = {http://www.jcb.org/cgi/content/abstract/151/4/763}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/11076962}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=11076962}, day = {13}, doi = {10.1083/jcb.151.4.763}, journal = {J. Cell Biol.}, keywords = {g0}, month = {November}, number = {4}, pages = {763--778}, posted-at = {2008-06-24 00:56:32}, priority = {2}, title = {Protein Kinase C Signaling Mediates a Program of Cell Cycle Withdrawal in the Intestinal Epithelium}, url = {http://dx.doi.org/10.1083/jcb.151.4.763}, volume = {151}, year = {2000} }

TY - JOUR ID - citeulike:2919903 L3 - citeulike-article-id:2919903 N2 - Members of the protein kinase C (PKC) family of signal transduction molecules have been widely implicated in regulation of cell growth and differentiation, although the underlying molecular mechanisms involved remain poorly defined. Using combined in vitro and in vivo intestinal epithelial model systems, we demonstrate that PKC signaling can trigger a coordinated program of molecular events leading to cell cycle withdrawal into G0. PKC activation in the IEC-18 intestinal crypt cell line resulted in rapid downregulation of D-type cyclins and differential induction of p21waf1/cip1 and p27kip1, thus targeting all of the major G1/S cyclin-dependent kinase complexes. These events were associated with coordinated alterations in expression and phosphorylation of the pocket proteins p107, pRb, and p130 that drive cells to exit the cell cycle into G0 as indicated by concomitant downregulation of the DNA licensing factor cdc6. Manipulation of PKC isozyme levels in IEC-18 cells demonstrated that PKC{alpha} alone can trigger hallmark events of cell cycle withdrawal in intestinal epithelial cells. Notably, analysis of the developmental control of cell cycle regulatory molecules along the crypt-villus axis revealed that PKC{alpha} activation is appropriately positioned within intestinal crypts to trigger this program of cell cycle exit-specific events in situ. Together, these data point to PKC{alpha} as a key regulator of cell cycle withdrawal in the intestinal epithelium. 10.1083/jcb.151.4.763 IS - 4 JF - J. Cell Biol. EP - 778 TI - Protein Kinase C Signaling Mediates a Program of Cell Cycle Withdrawal in the Intestinal Epithelium VL - 151 SP - 763 KW - g0 AU - Frey, Mark AU - Clark, Jennifer AU - Leontieva, Olga AU - Uronis, Joshua AU - Black, Adrian AU - Black, Jennifer PY - 2000/11/13/ UR - http://dx.doi.org/10.1083/jcb.151.4.763 ER -