title: Orthologous relationship of obscurin and Unc-89: phylogeny of a novel family of tandem myosin light chain kinases.
abstract: Myosin light chain kinases (MLCK) are a family of signaling proteins that are required for cytoskeletal remodeling in myocytes. Recently, two novel MLCK proteins, SPEG and obscurin-MLCK, were identified with the unique feature of two tandemly-arranged MLCK domains. In this study, the evolutionary origins of this MLCK subfamily were traced to a probable orthologue of obscurin-MLCK in Drosophila melanogaster, Drosophila Unc-89, and the MLCK kinase domains of zebrafish SPEG, zebrafish obscurin-MLCK, and human SPEG were characterized. Phylogenetic analysis of the MLCK domains indicates that the carboxy terminal kinase domains of obscurin-MLCK, SPEG and Unc-89 are more closely related to each other than to the amino terminal kinase domains or to other MLCKs, supporting the assertion that obscurin-MLCK is the vertebrate orthologue of Caenorhabditis elegans Unc-89, a giant multidomain protein that is required for normal myofibril assembly. The apparent lack of an invertebrate orthologue of SPEG and the conserved exon structure of the kinase domains between SPEG and obscurin-MLCK suggests that SPEG arose from obscurin-MLCK by a gene duplication event. The length of the primary amino acid sequence between the immunoglobulin (Ig) domains associated with the MLCK motifs is conserved in obscurin-MLCK, SPEG and C. elegans Unc-89, suggesting that these putative protein interaction domains may target the kinases to highly conserved intracellular sites. The conserved arrangement of the tandem MLCK domains and their relatively restricted expression in striated muscle indicates that further characterization of this novel MLCK subfamily may yield important insights into cardiac and skeletal muscle physiology.
authors.affiliation: Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, University of Michigan, 1242 Women's Hospital, 1500 E. Medical Center Dr., Ann Arbor, MI 48109, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Sutter
authors.forename: Maide O
authors.initials: MO
authors.lastname: Raeker
authors.forename: Andrei B
authors.initials: AB
authors.lastname: Borisov
authors.forename: Mark W
authors.initials: MW
authors.lastname: Russell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D016000:Cluster Analysis; D017931:DNA Primers; D019143:Evolution, Molecular; D040461:Gene Components; D020440:Gene Duplication; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D007448:Invertebrates / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics*; D009210:Myofibrils / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000235:genetics*; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases; D064067:Rho Guanine Nucleotide Exchange Factors; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014714:Vertebrates / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D020662:Guanine Nucleotide Exchange Factors; D009124:Muscle Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C098932:Unc-89 protein, C elegans; D029961:Zebrafish Proteins; C513831:obscna protein, zebrafish; C578224:OBSCN protein, human; D017346:Protein Serine-Threonine Kinases; D009219:Myosin-Light-Chain Kinase