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 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 Gubina, E. Articles by Mufson, R. A. Search for Related Content PubMed PubMed Citation Articles by Gubina, E. Articles by Mufson, R. A.

c Cytokine Receptor-Induced Stimulation of cAMP Response Element Binding Protein Phosphorylation Requires Protein Kinase C In Myeloid Cells: A Novel Cytokine Signal Transduction Cascade¹

Elaina Gubina^2,*, Xu Luo^2,*, E. Kwon, Kathleen Sakamoto, Yu Fang Shi^* and R. Allan Mufson^4,*

^* Department of Immunology, Holland Laboratory/American Red Cross, Rockville, MD 20855; Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, CA 90095

We have recently shown that IL-3R occupancy activates a phosphatidylcholine-specific phospholipase C, and the sustained diacylglycerol accumulation subsequently activates protein kinase C (PKC). In human IL-3-dependent myeloid cells (TF-1), the novel PKC isoform regulates bcl-2 expression and cell survival. The report of a PKC activatable cAMP response element (CRE) in the bcl-2 promoter and a role for PKC in bcl-2 expression in B cells led us to the hypothesis that PKC phosphorylation activates transcription factor CREB after IL-3R engagement. We found that IL-3 and GM-CSF induced phosphorylation of CREB on Ser¹³³ in TF-1 cells, and this phosphorylation was blocked by two structurally unrelated classes of PKC inhibitors. An inhibitor of cyclic nucleotide-dependent kinases did not block this phosphorylation. IL-4, which is biologically active in these cells but does not use the common subunit, did not phosphorylate CREB on Ser¹³³. Inhibition of mitogen-activated protein kinase kinase activity also inhibited IL3-induced CREB phosphorylation. The PKC inhibitors, but not a cyclic nucleotide-dependent kinase inhibitor, blocked IL-3 activation of CRE-dependent transcription from an egr-1 promoter/chloramphenicol acetyltransferase (CAT) reporter construction transiently transfected into TF-1 cells. Finally, TF-1 cells stably overexpressing PKC, but not the isoform of PKC, enhanced CRE-dependent CAT expression from the promoter/reporter construction. Therefore, it is likely that a PKC kinase cascade resulting in CREB phosphorylation represents a novel signal transduction cascade for regulating cellular gene expression through the common cytokine receptor.

This article has been cited by other articles:

				H.-C. Chen, J. C. Byrd, and N. Muthusamy Differential Role for Cyclic AMP Response Element Binding Protein-1 in Multiple Stages of B Cell Development, Differentiation, and Survival J. Immunol., February 15, 2006; 176(4): 2208 - 2218. [Abstract] [Full Text] [PDF]

				J. T. Blois, J. M. Mataraza, I. Mecklenbrauker, A. Tarakhovsky, and T. C. Chiles B Cell Receptor-induced cAMP-response Element-binding Protein Activation in B Lymphocytes Requires Novel Protein Kinase C{delta} J. Biol. Chem., July 16, 2004; 279(29): 30123 - 30132. [Abstract] [Full Text] [PDF]

				S. Paruchuri and A. Sjolander Leukotriene D4 Mediates Survival and Proliferation via Separate but Parallel Pathways in the Human Intestinal Epithelial Cell Line Int 407 J. Biol. Chem., November 14, 2003; 278(46): 45577 - 45585. [Abstract] [Full Text] [PDF]

				P. Mora-Garcia, J. Cheng, H. N. Crans-Vargas, A. Countouriotis, D. Shankar, and K. M. Sakamoto Transcriptional Regulators and Myelopoiesis: The Role of Serum Response Factor and CREB as Targets of Cytokine Signaling Stem Cells, March 1, 2003; 21(2): 123 - 130. [Abstract] [Full Text] [PDF]