title: Role of tyrosine phosphorylation in the regulation of the interaction of heterogenous nuclear ribonucleoprotein K protein with its protein and RNA partners.
abstract: 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 H(2)O(2)/Na(3)VO(4), 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.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ostrowski
authors.forename: D S
authors.initials: DS
authors.lastname: Schullery
authors.forename: O N
authors.initials: ON
authors.lastname: Denisenko
authors.forename: Y
authors.initials: Y
authors.lastname: Higaki
authors.forename: J
authors.initials: J
authors.lastname: Watts
authors.forename: R
authors.initials: R
authors.lastname: Aebersold
authors.forename: L
authors.initials: L
authors.lastname: Stempka
authors.forename: M
authors.initials: M
authors.lastname: Gschwendt
authors.forename: K
authors.initials: K
authors.lastname: Bomsztyk
mesh_terms: D006367:HeLa Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; C072074:HNRNPK protein, human; D014443:Tyrosine; D012313:RNA; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases