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 proteins, termed "the LBR complex." This complex includes the lamin B receptor protein (LBR or p58), a kinase which phosphorylates LBR in a constitutive fashion (LBR kinase), the nuclear lamins A and B, an 18-kDa polypeptide (p18), and a 34-kDa protein (p34/p32). The latter polypeptide has been shown to interact with the HIV-1 proteins Rev and Tat and with the splicing factor 2 (SF2). Using recombinant proteins produced in bacteria and synthetic peptides representing different regions of LBR, we now show that the LBR kinase modifies specifically arginine-serine (RS) dipeptide motifs located at the nucleoplasmic, NH2-terminal domain of LBR and in members of the SR family of splicing factors. Furthermore, we show that the NH2-terminal domain of LBR binds to p34/p32, whereas a mutated domain lacking the RS region does not. Phosphorylation of LBR by the RS kinase completely abolishes binding of p34/p32, suggesting that this enzyme regulates interactions among the components of the LBR complex.
Nikolakaki
E
E
Laboratory of Biochemistry, Faculty of Chemistry, The Aristotelian University of Thessaloniki, 54006 Thessaloniki, Greece.
Simos
G
G
Georgatos
S D
SD
Giannakouros
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D002451:Cell Compartmentation; D004912:Erythrocytes / Q000648:ultrastructure; D034921:Lamin Type B; D034882:Lamins; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000201:enzymology*; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014422:Turkeys; D000097682:Lamin B Receptor
D001120:Arginine; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D010455:Peptides; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor