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

J. Biol. Chem., Vol. 279, Issue 52, 54398-54404, December 24, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/52/54398    most recent M409579200v1 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 Haegebarth, A. Articles by Tyner, A. L. Search for Related Content PubMed PubMed Citation Articles by Haegebarth, A. Articles by Tyner, A. L. Social Bookmarking                      What's this?

The Nuclear Tyrosine Kinase BRK/Sik Phosphorylates and Inhibits the RNA-binding Activities of the Sam68-like Mammalian Proteins SLM-1 and SLM-2^*

Andrea Haegebarth, Darien Heap¶||, Wenjun Bie, Jason J. Derry, Stéphane Richard**, and Angela L. Tyner¶

From the Departments of Biochemistry and Molecular Genetics and ^¶Medicine, University of Illinois, Chicago, Illinois 60607 and ^**Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Departments of Oncology and Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada

Expression of the intracellular tyrosine kinase BRK/Sik is epithelial-specific and regulated during differentiation. Only a few substrates have been identified for BRK/Sik, including the KH domain containing RNA-binding protein Sam68 and the novel adaptor protein BKS. Although the physiological role of Sam68 is unknown, it has been shown to regulate mRNA transport, pre-mRNA splicing, and polyadenylation. Here we demonstrate that the Sam68-like mammalian proteins SLM-1 and SLM-2 but not the related KH domain containing heterogeneous nuclear ribonucleoprotein K are novel substrates of BRK/Sik. The expression of active BRK/Sik results in increased SLM-1 and SLM-2 phosphorylation and increased retention of BRK/Sik within the nucleus. The phosphorylation of SLM-1 and SLM-2 has functional relevance and leads to inhibition of their RNA-binding abilities. We show that SLM-1, SLM-2, and BRK/Sik have restricted patterns of expression unlike the ubiquitously expressed Sam68. Moreover, BRK/Sik, SLM-1, and Sam68 transcripts were coexpressed in the mouse gastrointestinal tract and skin, suggesting that SLM-1 and Sam68 could be physiologically relevant BRK/Sik targets in vivo. The ability of BRK/Sik to negatively regulate the RNA-binding activities of the KH domain RNA binding proteins SLM-1 and Sam68 may have an impact on the posttranscriptional regulation of epithelial cell gene expression.

Received for publication, August 20, 2004 , and in revised form, September 29, 2004.

^* This work was supported in part by National Institutes of Health Grant DK44525 and Department of Defense Army Grant DAMD17-01-1-0273 (to A. L. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by the German Academic Exchange Service (DAAD) and the Schering Foundation.

^|| Supported by National Institutes of Health Training Grant DK07788.

Supported by Grant MT-13377 from the Canadian Institutes of Health Research and a grant from the Cancer Research Society, Inc.

To whom correspondence should be addressed: University of Illinois College of Medicine, Department of Biochemistry and Molecular Genetics, M/C 669, 900 S. Ashland Ave., Chicago, IL 60607. Tel.: 312-996-7964; Fax: 312-413-0353; E-mail: atyner{at}uic.edu.

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

This article has been cited by other articles:

				G. Ohno, M. Hagiwara, and H. Kuroyanagi STAR family RNA-binding protein ASD-2 regulates developmental switching of mutually exclusive alternative splicing in vivo Genes & Dev., February 1, 2008; 22(3): 360 - 374. [Abstract] [Full Text] [PDF]

				M. G. Suzuki, S. Imanishi, N. Dohmae, T. Nishimura, T. Shimada, and S. Matsumoto Establishment of a Novel In Vivo Sex-Specific Splicing Assay System To Identify a trans-Acting Factor That Negatively Regulates Splicing of Bombyx mori dsx Female Exons Mol. Cell. Biol., January 1, 2008; 28(1): 333 - 343. [Abstract] [Full Text] [PDF]

				J. H. Ostrander, A. R. Daniel, K. Lofgren, C. G. Kleer, and C. A. Lange Breast Tumor Kinase (Protein Tyrosine Kinase 6) Regulates Heregulin-Induced Activation of ERK5 and p38 MAP Kinases in Breast Cancer Cells Cancer Res., May 1, 2007; 67(9): 4199 - 4209. [Abstract] [Full Text] [PDF]

				A. Haegebarth, W. Bie, R. Yang, S. E. Crawford, V. Vasioukhin, E. Fuchs, and A. L. Tyner Protein tyrosine kinase 6 negatively regulates growth and promotes enterocyte differentiation in the small intestine. Mol. Cell. Biol., July 1, 2006; 26(13): 4949 - 4957. [Abstract] [Full Text] [PDF]

				M. Kasprzycka, M. Majewski, Z.-J. Wang, A. Ptasznik, M. Wysocka, Q. Zhang, M. Marzec, P. Gimotty, M. R. Crompton, and M. A. Wasik Expression and Oncogenic Role of Brk (PTK6/Sik) Protein Tyrosine Kinase in Lymphocytes Am. J. Pathol., May 1, 2006; 168(5): 1631 - 1641. [Abstract] [Full Text] [PDF]

				K. E. Lukong, D. Larocque, A. L. Tyner, and S. Richard Tyrosine Phosphorylation of Sam68 by Breast Tumor Kinase Regulates Intranuclear Localization and Cell Cycle Progression J. Biol. Chem., November 18, 2005; 280(46): 38639 - 38647. [Abstract] [Full Text] [PDF]

				C. D. Cohen, P. P. Doran, S. M. Blattner, M. Merkle, G. Q. Wang, H. Schmid, P. W. Mathieson, M. A. Saleem, A. Henger, M. P. Rastaldi, et al. Sam68-Like Mammalian Protein 2, Identified by Digital Differential Display as Expressed by Podocytes, Is Induced in Proteinuria and Involved in Splice Site Selection of Vascular Endothelial Growth Factor J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1958 - 1965. [Abstract] [Full Text] [PDF]

				P. Zhang, J. H. Ostrander, E. J. Faivre, A. Olsen, D. Fitzsimmons, and C. A. Lange Regulated Association of Protein Kinase B/Akt with Breast Tumor Kinase J. Biol. Chem., January 21, 2005; 280(3): 1982 - 1991. [Abstract] [Full Text] [PDF]