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

J. Biol. Chem., Vol. 282, Issue 46, 33776-33787, November 16, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/46/33776    most recent M703320200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, D. Articles by Newton, A. C. Search for Related Content PubMed PubMed Citation Articles by Chen, D. Articles by Newton, A. C. Social Bookmarking                      What's this?

Amplitude Control of Protein Kinase C by RINCK, a Novel E3 Ubiquitin Ligase^*

Dan Chen¹, Christine Gould^¶, Renee Garza^||, Tianyan Gao², Randolph Y. Hampton^||, and Alexandra C. Newton³

From the Department of Pharmacology, Molecular Pathology Graduate Program, ^¶Biomedical Sciences Graduate Program, ^||Division of Biology, University of California at San Diego, La Jolla, California 92093-0721

Protein kinase C (PKC) isozymes play a central role in cellular signaling. Levels of PKC control the amplitude of agonist-induced signaling and alterations in these levels are associated with disease states, most notably cancer, yet mechanisms that control the turnover of the protein are poorly understood. Here we identify an E3 ligase that catalyzes the ubiquitin-mediated degradation of PKC. Specifically, we identified a RING finger domain-containing protein, RINCK (for RING-finger protein that interacts with C kinase) from a yeast two-hybrid screen using the amino terminus of PKC as bait. RINCK encodes a protein of 581 amino acids that contains a RING finger domain, a B-box, and two coiled-coil regions, the three domains that form the signature motif of the large family of diverse TRIM (tripartite motif) proteins. Co-immunoprecipitation studies using tsA201 cells reveal that RINCK and PKC associate with each other in cells. Studies using fragments of PKC reveal that this interaction is mediated by the C1A domain of PKC. RINCK induces the ubiquitination of PKC both in vitro and in cells. Overexpression of RINCK reduces the levels of PKC in cells, whereas genetic knockdown of endogenous RINCK increases the levels of PKC. This increase was observed for all PKC isozymes examined (including conventional, novel, and atypical). The RINCK-mediated degradation of PKC occurs independently of the classic phorbol ester-mediated down-regulation: genetic depletion of RINCK had no effect on the phorbol ester-mediated down-regulation and, additionally, up-regulated the levels of isozymes that cannot bind phorbol esters. Our data reveal a novel mechanism that provides amplitude control in PKC signaling through ubiquitination catalyzed by RINCK, an E3 ligase that specifically recognizes the C1 domain of PKC isoforms.

Received for publication, April 20, 2007 , and in revised form, September 14, 2007.

^* This work was supported by National Institutes of Health Grant P01 DK54441 (to A. C. N.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Dept. of Genetics, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, MA 02115.

² Present address: Dept. of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1048.

³ To whom correspondence should be addressed: 9500 Gilman Dr., La Jolla, CA 92093-0721. Tel.: 858-534-4527; Fax: 858-822-5888; E-mail: anewton{at}ucsd.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Y. Chow, C. Y. Yu, and G. R. Guy Sprouty2 Interacts with Protein Kinase C{delta} and Disrupts Phosphorylation of Protein Kinase D1 J. Biol. Chem., July 17, 2009; 284(29): 19623 - 19636. [Abstract] [Full Text] [PDF]

				A. Mashukova, A. S. Oriolo, F. A. Wald, M. L. Casanova, C. Kroger, T. M. Magin, M. B. Omary, and P. J. I. Salas Rescue of atypical protein kinase C in epithelia by the cytoskeleton and Hsp70 family chaperones J. Cell Sci., July 15, 2009; 122(14): 2491 - 2503. [Abstract] [Full Text] [PDF]

				C. Hellberg, C. Schmees, S. Karlsson, A. Ahgren, and C.-H. Heldin Activation of Protein Kinase C {alpha} Is Necessary for Sorting the PDGF {beta}-Receptor to Rab4a-dependent Recycling Mol. Biol. Cell, June 15, 2009; 20(12): 2856 - 2863. [Abstract] [Full Text] [PDF]

				M. A. Shatos, R. R. Hodges, Y. Oshi, J. A. Bair, D. Zoukhri, C. Kublin, K. Lashkari, and D. A. Dartt Role of cPKC{alpha} and nPKC{epsilon} in EGF-Stimulated Goblet Cell Proliferation Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 614 - 620. [Abstract] [Full Text] [PDF]

				Y. Pu, S. H. Garfield, N. Kedei, and P. M. Blumberg Characterization of the Differential Roles of the Twin C1a and C1b Domains of Protein Kinase C{delta} J. Biol. Chem., January 9, 2009; 284(2): 1302 - 1312. [Abstract] [Full Text] [PDF]