Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM protein.
In this report we have characterized a novel, ubiquitously expressed kinase, Clik1, that is predominantly nuclear and undergoes autophosphorylation. Yeast two-hybrid analysis indicated a highly specific association between Clik1 and CLP-36, which was identified in 36 out of 37 Clik1-interacting clones. CLP-36 is a PDZ-LIM protein that localizes to actin stress fibers in nonmuscle cells and associates with alpha-actinin via its PDZ-domain. The association of CLP-36 with Clik1, in turn, is mediated by the C-terminal part of CLP-36 containing the LIM domain, and association was not noted with the closely related ALP PDZ-LIM protein. Interestingly, the association with CLP-36 led to relocalization of the otherwise nuclear Clik1 kinase to actin stress fibers, where it disrupted the periodic staining pattern of CLP-36. Taken together these results establish the CLP-36 PDZ-LIM protein as an adapter, recruiting the Clik1 kinase to actin stress fibers in nonmuscle cells, and suggest that Clik1 represents a novel regulator of actin stress fibers.
Vallenius
Tea
T
Haartman Institute and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. Box 63, 00014 University of Helsinki, Finland.
Mäkelä
Tomi P
TP
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D003001:Cloning, Molecular; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D009928:Organ Specificity; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022502:Stress Fibers / Q000201:enzymology* / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D000199:Actins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; C097168:Pdlim1 protein, rat; D012333:RNA, Messenger; D010770:Phosphotransferases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C470368:STK35 protein, human