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

J. Biol. Chem., Vol. 277, Issue 49, 47052-47060, December 6, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/49/47052    most recent M205374200v1 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 Li, K. Articles by Wojchowski, D. M. Search for Related Content PubMed PubMed Citation Articles by Li, K. Articles by Wojchowski, D. M. Social Bookmarking                      What's this?

DYRK3 Activation, Engagement of Protein Kinase A/cAMP Response Element-binding Protein, and Modulation of Progenitor Cell Survival^*

Ke Li, Shuqing Zhao, Vinit Karur, and Don M. Wojchowski

From the Immunobiology Program and the Department of Veterinary Science, Pennsylvania State University, University Park, Pennsylvania 16802

DYRKs are a new family of dual-specificity tyrosine-regulated kinases with emerging roles in cell growth and development. Recently, we discovered that DYRK3 is expressed primarily in erythroid progenitor cells and modulates late erythropoiesis. We now describe 1) roles for the DYRK3 YTY signature motif in kinase activation, 2) the coupling of DYRK3 to cAMP response element (CRE)-binding protein (CREB), and 3) effects of DYRK3 on hematopoietic progenitor cell survival. Regarding the DYRK3 kinase domain, intactness of Tyr³³³ (but not Tyr³³¹) within subdomain loop VII-VIII was critical for activation. Tyr³³¹ plus Tyr³³³ acidification (Tyr mutated to Glu) was constitutively activating, but kinase activity was not affected substantially by unique N- or C-terminal domains. In transfected 293 and HeLa cells, DYRK3 was discovered to efficiently stimulate CRE-luciferase expression, to activate a CREB-Gal4 fusion protein, and to promote CREB phosphorylation at Ser¹³³. Interestingly, this CREB/CRE response was also supported (50% of wild-type activity) by a kinase-inactive DYRK3 mutant as well as a DYRK3 C-terminal region and was blocked by protein kinase A inhibitors, suggesting functional interactions between protein kinase A and DYRK3. Finally, DYRK3 expression in cytokine-dependent hematopoietic FDCW2 cells was observed to inhibit programmed cell death. Thus, primary new insight into DYRK3 kinase signaling routes, subdomain activities, and possible biofunctions is provided.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				X. Deng, D. Z. Ewton, and E. Friedman Mirk/Dyrk1B Maintains the Viability of Quiescent Pancreatic Cancer Cells by Reducing Levels of Reactive Oxygen Species Cancer Res., April 15, 2009; 69(8): 3317 - 3324. [Abstract] [Full Text] [PDF]

				O. Bogacheva, O. Bogachev, M. Menon, A. Dev, E. Houde, E. I. Valoret, H. M. Prosser, C. L. Creasy, S. J. Pickering, E. Grau, et al. DYRK3 Dual-specificity Kinase Attenuates Erythropoiesis during Anemia J. Biol. Chem., December 26, 2008; 283(52): 36665 - 36675. [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]

				X. Deng, S. E. Mercer, S. Shah, D. Z. Ewton, and E. Friedman The Cyclin-dependent Kinase Inhibitor p27Kip1 Is Stabilized in G0 by Mirk/dyrk1B Kinase J. Biol. Chem., May 21, 2004; 279(21): 22498 - 22504. [Abstract] [Full Text] [PDF]