A NUCLEAR ENVELOPE-ASSOCIATED KINASE PHOSPHORYLATES ARGININE-SERINE MOTIFS AND MODULATES INTERACTIONS BETWEEN THE LAMIN-B RECEPTOR AND OTHER NUCLEAR PROTEINS

Previous studies have identified a subassembly of nuclear envelope pro teins, termed ''the LBR complex'' This complex includes the lamin B re ceptor protein (LBR or p58), a kinase which phosphorylates LBR in a co nstitutive fashion (LBR kinase), the nuclear lamins A and B, an 18-kDa polypeptide (p18), and a 34-kDa protein (p34/p32). The latter polypep tide has been shown to interact with the HIV-1 proteins Rev and Tat an d with the splicing factor 2 (SF2). Using recombinant proteins produce d in bacteria and synthetic peptides representing different regions of LBR, we now show that the LBR kinase modifies specifically arginine-s erine (RS) dipeptide motifs located at the nucleoplasmic, NH2-terminal domain of LBR and in members of the SR family of splicing factors. Fu rthermore, we show that the NH2-terminal domain of LBR binds to p34/p3 2, whereas a mutated domain lacking the RS region does not. Phosphoryl ation of LBR by the RS kinase completely abolishes binding of p34/p32, suggesting that this enzyme regulates interactions among the componen ts of the LBR complex.