| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Biochemistry |
Department of Medicine, School of Medicine and Molecular Biology Institute, University of California, Los Angeles, California 90095
Protein kinase C (PKC) is implicated in the regulation of a variety of important functions in small cell lung cancer (SCLC) cell lines, but the downstream signaling targets stimulated by PKCs in these cells remain poorly characterized. Here we report that treatment of the SCLC cell lines H 69, H 345, and H 510 with phorbol-12,13-dibutyrate (PDB) led to a rapid and striking activation of protein kinase D (PKD), a novel serine/threonine protein kinase distinct from all PKC isoforms. PKD activation induced by PDB in these SCLC cell lines was completely abrogated by treatment of the cells with the PKC inhibitor GF 109203X (GF I) at concentrations (0.5–2.5 µM) that did not inhibit PKD activity when added directly to the in vitro kinase assays. Treatment with the biologically active phorbol ester 12-O-tetradecanoylphorbol-13-acetate or with membrane-permeable diacylglycerols also stimulated PKD activation, which was also completely prevented by prior exposure of the cells to GF I. The PKC inhibitors Ro 31-8220 and Go 7874 also blocked PKD activation in response to PDB. Addition of the autocrine growth factor bombesin to cultures of H 345 cells induced significant PKD activation that also was prevented by GF I. Our results demonstrate, for the first time, the existence of a PKC/PKD pathway in SCLC cells and raise the possibility that PKD may be an important mediator of some of the biological responses elicited by PKC activation in SCLC cells.
This article has been cited by other articles:
|
|
 |
|
  T. Gudermann and S. Roelle Calcium-dependent growth regulation of small cell lung cancer cells by neuropeptides Endocr. Relat. Cancer, December 1, 2006; 13(4): 1069 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Aaltonen, J. Koivunen, M. Laato, and J. Peltonen Heterogeneity of Cellular Proliferation within Transitional Cell Carcinoma: Correlation of Protein Kinase C Alpha/betaI Expression and Activity J. Histochem. Cytochem., July 1, 2006; 54(7): 795 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rozengurt, O. Rey, and R. T. Waldron Protein Kinase D Signaling J. Biol. Chem., April 8, 2005; 280(14): 13205 - 13208. [Full Text] [PDF]
|
|
|
|
|
|
N. Cabrera-Poch, L. Sanchez-Ruiloba, M. Rodriguez-Martinez, and T. Iglesias Lipid Raft Disruption Triggers Protein Kinase C and Src-dependent Protein Kinase D Activation and Kidins220 Phosphorylation in Neuronal Cells J. Biol. Chem., July 2, 2004; 279(27): 28592 - 28602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sinnett-Smith, E. Zhukova, N. Hsieh, X. Jiang, and E. Rozengurt Protein Kinase D Potentiates DNA Synthesis Induced by Gq-coupled Receptors by Increasing the Duration of ERK Signaling in Swiss 3T3 Cells J. Biol. Chem., April 16, 2004; 279(16): 16883 - 16893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rey, J. Yuan, S. H. Young, and E. Rozengurt Protein Kinase C{nu}/Protein Kinase D3 Nuclear Localization, Catalytic Activation, and Intracellular Redistribution in Response to G Protein-coupled Receptor Agonists J. Biol. Chem., June 20, 2003; 278(26): 23773 - 23785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yuan, L. W. Slice, J. Gu, and E. Rozengurt Cooperation of Gq, Gi, and G12/13 in Protein Kinase D Activation and Phosphorylation Induced by Lysophosphatidic Acid J. Biol. Chem., February 7, 2003; 278(7): 4882 - 4891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Waldron and E. Rozengurt Protein Kinase C Phosphorylates Protein Kinase D Activation Loop Ser744 and Ser748 and Releases Autoinhibition by the Pleckstrin Homology Domain J. Biol. Chem., January 3, 2003; 278(1): 154 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Guha, O. Rey, and E. Rozengurt Neurotensin Induces Protein Kinase C-dependent Protein Kinase D Activation and DNA Synthesis in Human Pancreatic Carcinoma Cell Line PANC-1 Cancer Res., March 1, 2002; 62(6): 1632 - 1640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Zhukova, J. Sinnett-Smith, and E. Rozengurt Protein Kinase D Potentiates DNA Synthesis and Cell Proliferation Induced by Bombesin, Vasopressin, or Phorbol Esters in Swiss 3T3 Cells J. Biol. Chem., October 19, 2001; 276(43): 40298 - 40305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yuan, L. W. Slice, and E. Rozengurt Activation of Protein Kinase D by Signaling through Rho and the alpha Subunit of the Heterotrimeric G Protein G13 J. Biol. Chem., October 12, 2001; 276(42): 38619 - 38627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Huang, A. J. Fleming, S. Wu, G. Virella, and M. F. Lopes-Virella Fc-{{gamma}} Receptor Cross-Linking by Immune Complexes Induces Matrix Metalloproteinase-1 in U937 Cells via Mitogen-Activated Protein Kinase Arterioscler. Thromb. Vasc. Biol., December 1, 2000; 20(12): 2533 - 2538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yuan, L. Slice, J. H. Walsh, and E. Rozengurt Activation of Protein Kinase D by Signaling through the alpha Subunit of the Heterotrimeric G Protein Gq J. Biol. Chem., January 21, 2000; 275(3): 2157 - 2164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sinnett-Smith, C. Santiskulvong, J. Duque, and E. Rozengurt [D-Arg1,D-Trp5,7,9,Leu11]Substance P Inhibits Bombesin-induced Mitogenic Signal Transduction Mediated by Both Gq and G12 in Swiss 3T3 Cells J. Biol. Chem., September 22, 2000; 275(39): 30644 - 30652. [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]
|
|
|
|
|
|
R. T. Waldron, O. Rey, T. Iglesias, T. Tugal, D. Cantrell, and E. Rozengurt Activation Loop Ser744 and Ser748 in Protein Kinase D Are Transphosphorylated in Vivo J. Biol. Chem., August 24, 2001; 276(35): 32606 - 32615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rey, S. H. Young, D. Cantrell, and E. Rozengurt Rapid Protein Kinase D Translocation in Response to G Protein-coupled Receptor Activation. DEPENDENCE ON PROTEIN KINASE C J. Biol. Chem., August 24, 2001; 276(35): 32616 - 32626. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Rey, J. Sinnett-Smith, E. Zhukova, and E. Rozengurt Regulated Nucleocytoplasmic Transport of Protein Kinase D in Response to G Protein-coupled Receptor Activation J. Biol. Chem., December 21, 2001; 276(52): 49228 - 49235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Waldron and E. Rozengurt Oxidative Stress Induces Protein Kinase D Activation in Intact Cells. INVOLVEMENT OF Src AND DEPENDENCE ON PROTEIN KINASE C J. Biol. Chem., May 26, 2000; 275(22): 17114 - 17121. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
