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J. Biol. Chem. 275 (5): 3619-3628

© 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

J Biol Chem, Vol. 275, Issue 5, 3619-3628, February 4, 2000

Role of Tyrosine Phosphorylation in the Regulation of the Interaction of Heterogenous Nuclear Ribonucleoprotein K Protein with Its Protein and RNA Partners*

Jerzy OstrowskiDagger §, Daniel S. SchulleryDagger , Oleg N. DenisenkoDagger , Yugi HigakiDagger , Julian Wattspar , Rudi Aebersoldpar , Luise Stempka**, Michael Gschwendt**, and Karol BomsztykDagger Dagger Dagger

From the Departments of Dagger  Medicine and par  Molecular Biotechnology, University of Washington, Seattle, Washington 98195, the ** German Cancer Research Center, D-69120 Heidelberg, Germany, and the § Department of Gastroenterology, Medical Center for Postgraduate Education at the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland

The heterogeneous nuclear ribonucleoprotein K protein recruits a diversity of molecular partners and may act as a docking platform involved in such processes as transcription, RNA processing, and translation. We show that K protein is tyrosine-phosphorylated in vitro by Src and Lck. Treatment with H2O2/Na3VO4, which induces oxidative stress, stimulated tyrosine phosphorylation of K protein in cultured cells and in intact livers. Tyrosine phosphorylation increased binding of Lck and the proto-oncoprotein Vav to K protein in vitro. Oxidative stress increased the association of K protein with Lck and Vav, suggesting that tyrosine phosphorylation regulates the ability of K protein to recruit these effectors in vivo. Translation-based assay showed that K protein is constitutively bound to many mRNAs in vivo. Native immunoprecipitated K protein-mRNA complexes were disrupted by tyrosine phosphorylation, suggesting that the in vivo binding of K protein to mRNA may be responsive to the extracellular signals that activate tyrosine kinases. This study shows that tyrosine phosphorylation of K protein regulates K protein-protein and K protein-RNA interactions. These data are consistent with a model in which functional interaction of K protein is responsive to changes in the extracellular environment. Acting as a docking platform, K protein may bridge signal transduction pathways to sites of nucleic acid-dependent process such as transcription, RNA processing, and translation.

* This work was supported by National Institutes of Health (NIH) Grants GM45134 and DK45978, the Northwest Kidney Foundation, a NATO International Collaboration grant (to K. B.), and NIH Grant AI 41109 (to R. A.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by the Yamagiwa-Yoshida Memorial International Cancer Study Grant from the International Union Against Cancer.

Dagger Dagger To whom correspondence should be addressed: Dept. of Medicine, Box 356521, University of Washington, Seattle, WA 98195. Tel.: 206-543-3792; Fax: 206-685-8661; E-mail: karolb@u.washington.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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