Tyrosine phosphorylation mediated by Src-family kinases in the nucleus

Protein-tyrosine phosphorylation is regulated by protein-tyrosine kinases (PTK) and protein-tyrosine phosphatases (PTP). Certain types of PTKs have recently been reported to localize to the nucleus. However, less is known about the function of PTKs in the nucleus. We show here that Src-family protein-tyrosine kinases (SFKs) that are localized in the nucleus are involved in induction of nuclear tyrosine phosphorylation. We examined a role of Lyn, a member of SFKs, in the nucleus and constructed two nucleus-targeted kinase-active Lyn (NLS-Lyn) and kinase-inactive Lyn (NLS-Lyn (KD)). Both of these Lyn mutants induced growth inhibition. Expression of NLS-Lyn brought about aberrant DNA condensation and disorganization of the nucleolus. Expression of NLS-Lyn (KD) brought about lobulation of the nucleus. These results suggest that tyrosine phosphorylation in the nucleus induced by Lyn is involved in cell growth and maintenance of nuclear morphology.