title: Substrate profiling of human vaccinia-related kinases identifies coilin, a Cajal body nuclear protein, as a phosphorylation target with neurological implications.
abstract: Protein phosphorylation by kinases plays a central role in the regulation and coordination of multiple biological processes. In general, knowledge on kinase specificity is restricted to substrates identified in the context of specific cellular responses, but kinases are likely to have multiple additional substrates and be integrated in signaling networks that might be spatially and temporally different, and in which protein complexes and subcellular localization can play an important role. In this report the substrate specificity of atypical human vaccinia-related kinases (VRK1 and VRK2) using a human peptide-array containing 1080 sequences phosphorylated in known signaling pathways has been studied. The two kinases identify a subset of potential peptide targets, all of them result in a consensus sequence composed of at least four basic residues in peptide targets. Linear peptide arrays are therefore a useful approach in the characterization of kinases and substrate identification, which can contribute to delineate the signaling network in which VRK proteins participate. One of these target proteins is coilin; a basic protein located in nuclear Cajal bodies. Coilin is phosphorylated in Ser184 by both VRK1 and VRK2. Coilin colocalizes and interacts with VRK1 in Cajal bodies, but not with the mutant VRK1 (R358X). VRK1 (R358X) is less active than VRK1. Altered regulation of coilin might be implicated in several neurological diseases such as ataxias and spinal muscular atrophies.
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas(CSIC)-Universidad de Salamanca, Salamanca 37007, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Sanz-García
authors.forename: Marta
authors.initials: M
authors.lastname: Vázquez-Cedeira
authors.forename: Efrat
authors.initials: E
authors.lastname: Kellerman
authors.forename: Paul
authors.initials: P
authors.lastname: Renbaum
authors.forename: Ephrat
authors.initials: E
authors.lastname: Levy-Lahad
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Lazo
mesh_terms: D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C068921:p80-coilin; D017346:Protein Serine-Threonine Kinases; C109890:VRK1 protein, human; C109891:VRK2 protein, human