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) 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hausser, A. Articles by Johannes, F.-J. Search for Related Content PubMed PubMed Citation Articles by Hausser, A. Articles by Johannes, F.-J.

J Biol Chem, Vol. 274, Issue 14, 9258-9264, April 2, 1999

Protein Kinase C µ Is Negatively Regulated by 14-3-3 Signal Transduction Proteins

Angelika Hausser, Peter Storz, Gisela Link, Hartmut Stoll, Yun-Cai Liu^§, Amnon Altman^§, Klaus Pfizenmaier, and Franz-Josef Johannes

From the  Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany and the ^§ Division of Cell Biology and Immunbiology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121

Recent studies have documented direct interaction between 14-3-3 proteins and key molecules in signal transduction pathways like Ras, Cbl, and protein kinases. In T cells, the 14-3-3 isoform has been shown to associate with protein kinase C  and to negatively regulate interleukin-2 secretion. Here we present data that 14-3-3 interacts with protein kinase C µ (PKCµ), a subtype that differs from other PKC members in structure and activation mechanisms. Specific interaction of PKCµ and 14-3-3 can be shown in the T cell line Jurkat by immunocoprecipitiation and by pulldown assays of either endogenous or overexpressed proteins using PKCµ-specific antibodies and GST-14-3-3 fusion proteins, respectively. Using PKCµ deletion mutants, the 14-3-3 binding region is mapped within the regulatory C1 domain. Binding of 14-3-3 to PKCµ is significantly enhanced upon phorbol ester stimulation of PKCµ kinase activity in Jurkat cells and occurs via a Cbl-like serine containing consensus motif. However, 14-3-3 is not a substrate of PKCµ. In contrast 14-3-3 strongly down-regulates PKCµ kinase activity in vitro. Moreover, overexpression of 14-3-3 significantly reduced phorbol ester induced activation of PKCµ kinase activity in intact cells. We therefore conclude that 14-3-3 is a negative regulator of PKCµ in T cells.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				H. Doppler and P. Storz A Novel Tyrosine Phosphorylation Site in Protein Kinase D Contributes to Oxidative Stress-mediated Activation J. Biol. Chem., November 2, 2007; 282(44): 31873 - 31881. [Abstract] [Full Text] [PDF]

				M. Alvarez, X. Altafaj, S. Aranda, and S. de la Luna DYRK1A Autophosphorylation on Serine Residue 520 Modulates Its Kinase Activity via 14-3-3 Binding Mol. Biol. Cell, April 1, 2007; 18(4): 1167 - 1178. [Abstract] [Full Text] [PDF]

				A. Hausser, G. Link, M. Hoene, C. Russo, O. Selchow, and K. Pfizenmaier Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III {beta} protects from dephosphorylation and stabilizes lipid kinase activity J. Cell Sci., September 1, 2006; 119(17): 3613 - 3621. [Abstract] [Full Text] [PDF]

				H. Tokumitsu, N. Hatano, H. Inuzuka, Y. Sueyoshi, S. Yokokura, T. Ichimura, N. Nozaki, and R. Kobayashi Phosphorylation of Numb Family Proteins: POSSIBLE INVOLVEMENT OF CA2+/CALMODULIN-DEPENDENT PROTEIN KINASES J. Biol. Chem., October 21, 2005; 280(42): 35108 - 35118. [Abstract] [Full Text] [PDF]

				W. Zhang, S. Zheng, P. Storz, and W. Min Protein Kinase D Specifically Mediates Apoptosis Signal-regulating Kinase 1-JNK Signaling Induced by H2O2 but Not Tumor Necrosis Factor J. Biol. Chem., May 13, 2005; 280(19): 19036 - 19044. [Abstract] [Full Text] [PDF]

				M. Ling, U. Troller, R. Zeidman, H. Stensman, A. Schultz, and C. Larsson Identification of Conserved Amino Acids N-terminal of the PKC{epsilon}C1b Domain Crucial for Protein Kinase C{epsilon}-mediated Induction of Neurite Outgrowth J. Biol. Chem., May 6, 2005; 280(18): 17910 - 17919. [Abstract] [Full Text] [PDF]

				S. Urschel, F. Bassermann, R.-Y. Bai, S. Munch, C. Peschel, and J. Duyster Phosphorylation of Grb10 Regulates Its Interaction with 14-3-3 J. Biol. Chem., April 29, 2005; 280(17): 16987 - 16993. [Abstract] [Full Text] [PDF]

				M. Jaggi, P. S. Rao, D. J. Smith, M. J. Wheelock, K. R. Johnson, G. P. Hemstreet, and K.C. Balaji E-Cadherin Phosphorylation by Protein Kinase D1/Protein Kinase C{micro} is Associated with Altered Cellular Aggregation and Motility in Prostate Cancer Cancer Res., January 15, 2005; 65(2): 483 - 492. [Abstract] [Full Text] [PDF]

				Y. Wang, N. Kedei, M. Wang, Q. J. Wang, A. R. Huppler, A. Toth, R. Tran, and P. M. Blumberg Interaction between Protein Kinase C{micro} and the Vanilloid Receptor Type 1 J. Biol. Chem., December 17, 2004; 279(51): 53674 - 53682. [Abstract] [Full Text] [PDF]

				M. A. Davare, T. Saneyoshi, E. S. Guire, S. C. Nygaard, and T. R. Soderling Inhibition of Calcium/Calmodulin-dependent Protein Kinase Kinase by Protein 14-3-3 J. Biol. Chem., December 10, 2004; 279(50): 52191 - 52199. [Abstract] [Full Text] [PDF]

				T. A. Nguyen, L. J. Takemoto, and D. J. Takemoto Inhibition of Gap Junction Activity through the Release of the C1B Domain of Protein Kinase C{gamma} (PKC{gamma}) from 14-3-3: IDENTIFICATION OF PKC{gamma}-BINDING SITES J. Biol. Chem., December 10, 2004; 279(50): 52714 - 52725. [Abstract] [Full Text] [PDF]

				P. Storz, H. Doppler, and A. Toker Activation Loop Phosphorylation Controls Protein Kinase D-Dependent Activation of Nuclear Factor {kappa}B Mol. Pharmacol., October 1, 2004; 66(4): 870 - 879. [Abstract] [Full Text] [PDF]

				Q. Zheng, G. Yin, C. Yan, M. Cavet, and B. C. Berk 14-3-3{beta} Binds to Big Mitogen-activated Protein Kinase 1 (BMK1/ERK5) and Regulates BMK1 Function J. Biol. Chem., March 5, 2004; 279(10): 8787 - 8791. [Abstract] [Full Text] [PDF]

				G. K. Kumar and J. B. Klein Analysis of expression and posttranslational modification of proteins during hypoxia J Appl Physiol, March 1, 2004; 96(3): 1178 - 1186. [Abstract] [Full Text] [PDF]

				N. H. Barmack, T. R. Bilderback, H. Liu, Z. Qian, and V. Yakhnitsa Activity-Dependent Expression of Acyl-Coenzyme A-Binding Protein in Retinal Muller Glial Cells Evoked by Optokinetic Stimulation J. Neurosci., February 4, 2004; 24(5): 1023 - 1033. [Abstract] [Full Text] [PDF]

				S. B. Kennett, J. D. Roberts, and K. Olden Requirement of Protein Kinase C{micro} Activation and Calpain-mediated Proteolysis for Arachidonic Acid-stimulated Adhesion of MDA-MB-435 Human Mammary Carcinoma Cells to Collagen Type IV J. Biol. Chem., January 30, 2004; 279(5): 3300 - 3307. [Abstract] [Full Text] [PDF]

				M. E. Cavet, S. Lehoux, and B. C. Berk 14-3-3beta Is a p90 Ribosomal S6 Kinase (RSK) Isoform 1-binding Protein That Negatively Regulates RSK Kinase Activity J. Biol. Chem., May 9, 2003; 278(20): 18376 - 18383. [Abstract] [Full Text] [PDF]

				H. Onuma, H. Osawa, K. Yamada, T. Ogura, F. Tanabe, D. K. Granner, and H. Makino Identification of the Insulin-Regulated Interaction of Phosphodiesterase 3B With 14-3-3 {beta} Protein Diabetes, December 1, 2002; 51(12): 3362 - 3367. [Abstract] [Full Text] [PDF]

				I. Brandlin, T. Eiseler, R. Salowsky, and F.-J. Johannes Protein Kinase C{micro} Regulation of the JNK Pathway Is Triggered via Phosphoinositide-dependent Kinase 1 and Protein Kinase Cepsilon J. Biol. Chem., November 15, 2002; 277(47): 45451 - 45457. [Abstract] [Full Text] [PDF]

				L. Gannon-Murakami and K. Murakami Selective Association of Protein Kinase C with 14-3-3 zeta in Neuronally Differentiated PC12 Cells. STIMULATORY AND INHIBITORY EFFECT OF 14-3-3 zeta IN VIVO J. Biol. Chem., June 21, 2002; 277(26): 23116 - 23122. [Abstract] [Full Text] [PDF]

				D. W. Powell, M. J. Rane, Q. Chen, S. Singh, and K. R. McLeish Identification of 14-3-3zeta as a Protein Kinase B/Akt Substrate J. Biol. Chem., June 7, 2002; 277(24): 21639 - 21642. [Abstract] [Full Text] [PDF]

				I. Brandlin, S. Hubner, T. Eiseler, M. Martinez-Moya, A. Horschinek, A. Hausser, G. Link, S. Rupp, P. Storz, K. Pfizenmaier, et al. Protein Kinase C (PKC)eta -mediated PKC{micro} Activation Modulates ERK and JNK Signal Pathways J. Biol. Chem., February 15, 2002; 277(8): 6490 - 6496. [Abstract] [Full Text] [PDF]

				Y. Wang, R. T. Waldron, A. Dhaka, A. Patel, M. M. Riley, E. Rozengurt, and J. Colicelli The RAS Effector RIN1 Directly Competes with RAF and Is Regulated by 14-3-3 Proteins Mol. Cell. Biol., February 1, 2002; 22(3): 916 - 926. [Abstract] [Full Text] [PDF]

				N. Brose and C. Rosenmund Move over protein kinase C, you've got company: alternative cellular effectors of diacylglycerol and phorbol esters J. Cell Sci., January 12, 2002; 115(23): 4399 - 4411. [Abstract] [Full Text] [PDF]

				J. Y. Toshima, J. Toshima, T. Watanabe, and K. Mizuno Binding of 14-3-3beta Regulates the Kinase Activity and Subcellular Localization of Testicular Protein Kinase 1 J. Biol. Chem., November 9, 2001; 276(46): 43471 - 43481. [Abstract] [Full Text] [PDF]

				S. A. Matthews, E. Rozengurt, and D. Cantrell Characterization of Serine 916 as an in Vivo Autophosphorylation Site for Protein Kinase D/Protein Kinase C{micro} J. Biol. Chem., September 10, 1999; 274(37): 26543 - 26549. [Abstract] [Full Text] [PDF]

				D. Vertommen, M. Rider, Y. Ni, E. Waelkens, W. Merlevede, J. R. Vandenheede, and J. Van Lint Regulation of Protein Kinase D by Multisite Phosphorylation. IDENTIFICATION OF PHOSPHORYLATION SITES BY MASS SPECTROMETRY AND CHARACTERIZATION BY SITE-DIRECTED MUTAGENESIS J. Biol. Chem., June 23, 2000; 275(26): 19567 - 19576. [Abstract] [Full Text] [PDF]

				K. Endo, E. Oki, V. Biedermann, H. Kojima, K. Yoshida, F.-J. Johannes, D. Kufe, and R. Datta Proteolytic Cleavage and Activation of Protein Kinase C {micro} by Caspase-3 in the Apoptotic Response of Cells to 1-beta -D-Arabinofuranosylcytosine and Other Genotoxic Agents J. Biol. Chem., June 9, 2000; 275(24): 18476 - 18481. [Abstract] [Full Text] [PDF]

				P. Storz, A. Hausser, G. Link, J. Dedio, B. Ghebrehiwet, K. Pfizenmaier, and F.-J. Johannes Protein Kinase C {micro} Is Regulated by the Multifunctional Chaperon Protein p32 J. Biol. Chem., August 4, 2000; 275(32): 24601 - 24607. [Abstract] [Full Text] [PDF]

				T. Iglesias, N. Cabrera-Poch, M. P. Mitchell, T. J. P. Naven, E. Rozengurt, and G. Schiavo Identification and Cloning of Kidins220, a Novel Neuronal Substrate of Protein Kinase D J. Biol. Chem., December 15, 2000; 275(51): 40048 - 40056. [Abstract] [Full Text] [PDF]

				A. Hausser, G. Link, L. Bamberg, A. Burzlaff, S. Lutz, K. Pfizenmaier, and F.-J. Johannes Structural requirements for localization and activation of protein kinase C {micro} (PKC{micro}) at the Golgi compartment J. Cell Biol., January 7, 2002; 156(1): 65 - 74. [Abstract] [Full Text] [PDF]

				R. Zeidman, U. Troller, A. Raghunath, S. Pahlman, and C. Larsson Protein Kinase Cepsilon Actin-binding Site Is Important for Neurite Outgrowth during Neuronal Differentiation Mol. Biol. Cell, January 1, 2002; 13(1): 12 - 24. [Abstract] [Full Text] [PDF]