CITRON RHO-INTERACTING KINASE, A NOVEL TISSUE-SPECIFIC SER THR KINASEENCOMPASSING THE RHO-RAC-BINDING PROTEIN CITRON/

We have identified a novel serine/threonine kinase belonging to the my otonic dystrophy kinase family. The kinase can be produced in at least two different isoforms: a similar to 240-kDa protein (Citron Rho-inte racting kinase, CRIK), in which the kinase domain is followed by the s equence of Citron, a previously identified Rho/Rac binding protein; a similar to 54-kDa protein (CRIK-short kinase (SK)), which consists mos tly of the kinase domain. CRIK and CRIK-SK proteins are capable of pho sphorylating exogenous substrates as well as of autophosphorylation, w hen tested by in vitro kinase assays after expression into COS7 cells. CRIK kinase activity is increased severalfold by coexpression of cost itutively active Rho, while active Rac has more limited effects. Kinas e activity of endogenous CRIK is indicated by in vitro kinase assays a fter immunoprecipitation with antibodies recognizing the Citron moiety of the protein. When expressed in keratinocytes, full-length CRIK but not CRIK-SK, localizes into corpuscular cytoplasmic structures and el icits recruitment of actin into these structures. The previously repor ted Rho-associated kinases ROCK I and II are ubiquitously expressed. I n contrast, CRIK exhibits a restricted pattern of expression, suggesti ng that this kinase may fulfill a more specialized function in specifi c cell types.