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 Ács, P. Articles by Blumberg, P. M. Search for Related Content PubMed PubMed Citation Articles by Ács, P. Articles by Blumberg, P. M. Social Bookmarking                      What's this?

Volume 272, Number 45, Issue of November 7, 1997 pp. 28793-28799
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Both the Catalytic and Regulatory Domains of Protein Kinase C Chimeras Modulate the Proliferative Properties of NIH 3T3 Cells

(Received for publication, July 7, 1997)

Péter Ács , Qiming J. Wang ^§ , Krisztina Bögi , Adriana M. Marquez , Patricia S. Lorenzo , Tamás Bíró , Zoltán Szállási ^¶ , J. Frederic Mushinski ^§ and Peter M. Blumberg

From the  Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, and ^§ Laboratory of Genetics, NCI, National Institutes of Health, Bethesda, Maryland 20892 and the ^¶ Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814

Protein kinase C (PKC) isozymes exhibit important differences in terms of their regulation and biological functions. Not only may some PKC isoforms be active and others not for a given response, but the actions of different isoforms may even be antagonistic. In NIH 3T3 cells, for example, PKC arrests cell growth whereas PKC stimulates it. To probe the contribution of the regulatory and the catalytic domains of PKC isozymes to isozyme-specific responses, we prepared chimeras between the regulatory and the catalytic domains of PKC, -, and -. These chimeras, which preserve the overall structure of the native PKC enzymes, were stably expressed in mouse fibroblasts. A major objective was to characterize the growth properties of the cells that overexpress the various PKC constructs. Our data demonstrate that both the regulatory and the catalytic domains play roles in cell proliferation. The regulatory domain of PKC enhanced cell growth in the absence or presence of phorbol 12-myristate 13-acetate (PMA), and, in the presence of PMA, all chimeras with the PKC regulatory domain also gave rise to colonies in soft agar; the role of the catalytic domain of PKC was evident in the PMA-treated cells that overexpressed the PKC chimera containing the  regulatory and the  catalytic domains (PKC/). The important contribution of the PKC catalytic domain to the growth of PKC/-expressing cells was also evident in terms of a significantly increased saturation density in the presence of PMA, their formation of foci upon PMA treatment, and the induction of anchorage-independent growth. Aside from the growth-promoting effect of PKC, we have shown that most chimeras with PKC and - regulatory domains inhibit cell growth. These results underscore the complex contributions of the regulatory and catalytic domains to the overall behavior of PKC.

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

This article has been cited by other articles:

				F. Xiao, J. R Puddefoot, S. Barker, and G. P Vinson Changes in angiotensin II type 1 receptor signalling pathways evoked by a monoclonal antibody raised to the N-terminus J. Endocrinol., April 1, 2008; 197(1): 25 - 33. [Abstract] [Full Text] [PDF]

				A. Denys, A. Hichami, and N. A. Khan n-3 PUFAs modulate T-cell activation via protein kinase C-{alpha} and -{varepsilon} and the NF-{kappa}B signaling pathway J. Lipid Res., April 1, 2005; 46(4): 752 - 758. [Abstract] [Full Text] [PDF]

				D. C. Braun, S. H. Garfield, and P. M. Blumberg Analysis by Fluorescence Resonance Energy Transfer of the Interaction between Ligands and Protein Kinase C{delta} in the Intact Cell J. Biol. Chem., March 4, 2005; 280(9): 8164 - 8171. [Abstract] [Full Text] [PDF]

				Q. J. Wang, G. Lu, W. A. Schlapkohl, A. Goerke, C. Larsson, H. Mischak, P. M. Blumberg, and J. F. Mushinski The V5 Domain of Protein Kinase C Plays a Critical Role in Determining the Isoform-Specific Localization, Translocation, and Biological Function of Protein Kinase C-{delta} and -{varepsilon} Mol. Cancer Res., February 1, 2004; 2(2): 129 - 140. [Abstract] [Full Text] [PDF]

				K. Page, J. Li, K. C. Corbit, K. M. Rumilla, J.-W. Soh, I. B. Weinstein, C. Albanese, R. G. Pestell, M. R. Rosner, and M. B. Hershenson Regulation of Airway Smooth Muscle Cyclin D1 Transcription by Protein Kinase C-{delta} Am. J. Respir. Cell Mol. Biol., August 1, 2002; 27(2): 204 - 213. [Abstract] [Full Text] [PDF]

				M. Blass, I. Kronfeld, G. Kazimirsky, P. M. Blumberg, and C. Brodie Tyrosine Phosphorylation of Protein Kinase C{delta} Is Essential for Its Apoptotic Effect in Response to Etoposide Mol. Cell. Biol., January 1, 2002; 22(1): 182 - 195. [Abstract] [Full Text] [PDF]

				T. A. Jackson, R. E. Schweppe, D. M. Koterwas, and A. P. Bradford Fibroblast Growth Factor Activation of the Rat PRL Promoter is Mediated by PKC{delta} Mol. Endocrinol., September 1, 2001; 15(9): 1517 - 1528. [Abstract] [Full Text] [PDF]

				R. Mandil, E. Ashkenazi, M. Blass, I. Kronfeld, G. Kazimirsky, G. Rosenthal, F. Umansky, P. S. Lorenzo, P. M. Blumberg, and C. Brodie Protein Kinase C{{alpha}} and Protein Kinase C{{delta}} Play Opposite Roles in the Proliferation and Apoptosis of Glioma Cells Cancer Res., June 1, 2001; 61(11): 4612 - 4619. [Abstract] [Full Text] [PDF]

				P. Acs, M. Beheshti, Z. Szallasi, L. Li, S. H. Yuspa, and P. M. Blumberg Effect of a tyrosine 155 to phenylalanine mutation of protein kinase C{delta} on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts Carcinogenesis, May 1, 2000; 21(5): 887 - 891. [Abstract] [Full Text] [PDF]

				C. A. Peters, E. T. Maizels, and M. Hunzicker-Dunn Activation of PKC delta in the Rat Corpus Luteum during Pregnancy. POTENTIAL ROLE OF PROLACTIN SIGNALING J. Biol. Chem., December 24, 1999; 274(52): 37499 - 37505. [Abstract] [Full Text] [PDF]

				S. C. Kiley, K. J. Clark, M. Goodnough, D. R. Welch, and S. Jaken Protein Kinase C {{delta}} Involvement in Mammary Tumor Cell Metastasis Cancer Res., July 1, 1999; 59(13): 3230 - 3238. [Abstract] [Full Text] [PDF]

				R. Zeidman, B. Lofgren, S. Pahlman, and C. Larsson PKCepsilon , Via its Regulatory Domain and Independently of its Catalytic Domain, Induces Neurite-like Processes in Neuroblastoma Cells J. Cell Biol., May 17, 1999; 145(4): 713 - 726. [Abstract] [Full Text] [PDF]

				C. Brodie, K. Bogi, P. Acs, P. S. Lorenzo, L. Baskin, and P. M. Blumberg Protein Kinase C delta  (PKCdelta ) Inhibits the Expression of Glutamine Synthetase in Glial Cells via the PKCdelta Regulatory Domain and Its Tyrosine Phosphorylation J. Biol. Chem., November 13, 1998; 273(46): 30713 - 30718. [Abstract] [Full Text] [PDF]

				I. Kronfeld, G. Kazimirsky, P. S. Lorenzo, S. H. Garfield, P. M. Blumberg, and C. Brodie Phosphorylation of Protein Kinase Cdelta on Distinct Tyrosine Residues Regulates Specific Cellular Functions J. Biol. Chem., November 3, 2000; 275(45): 35491 - 35498. [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]