title: Recruiting a silent partner for activation of the protein kinase SRPK1.
abstract: The SRPK family of protein kinases regulates mRNA splicing by phosphorylating an essential group of factors known as SR proteins, so named for a C-terminal domain enriched in arginine-serine dipeptide repeats (RS domains). SRPKs phosphorylate RS domains at numerous sites altering SR protein subcellular localization and splicing function. The RS domains in these splicing factors differ considerably in overall length and dipeptide layout. Despite their importance, little is known about how these diverse RS domains interact with SRPKs and regulate SR protein phosphorylation. We now show that sequences distal to the SRPK1 consensus region in the RS domain of the prototype SR protein SRSF1 are not passive as originally thought but rather play active roles in accelerating phosphorylation rates. Located in the C-terminal end of the RS domain, this nonconsensus region up-regulates rate-limiting ADP release through the nucleotide release factor, a structural module in SRPK1 composed of two noncontiguous sequence elements outside the kinase core domain. The data show that the RS domain in SRSF1 is multifunctional and that sequences once thought to be catalytically silent can be recruited to enhance the efficiency of SR protein phosphorylation.
authors.affiliation: Department of Pharmacology, University of California, San Diego , La Jolla, California 92093-0636, United States.
authors.forename: Brandon E
authors.initials: BE
authors.lastname: Aubol
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Adams
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012326:RNA Splicing / Q000502:physiology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000244:Adenosine Diphosphate; C087728:SRPK1 protein, human; D017346:Protein Serine-Threonine Kinases