Role of tyrosine phosphorylation in the regulation of the interaction of heterogenous nuclear ribonucleoprotein K protein with its protein and RNA partners.
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.
Ostrowski
J
J
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
Schullery
D S
DS
Denisenko
O N
ON
Higaki
Y
Y
Watts
J
J
Aebersold
R
R
Stempka
L
L
Gschwendt
M
M
Bomsztyk
K
K
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
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