LIMK-1 and LIMK-2, two members of a LIM motif-containing protein kinase family.
We previously isolated human cDNA encoding LIM-kinase (LIMK), a putative protein kinase which contains two repeats of the LIM motif at the N-terminus and a protein kinase consensus sequence at the C-terminus. Using as a probe a cDNA fragment of human LIMK, we isolated from a rat brain cDNA library cDNA clones encoding two distinct protein kinases (termed LIMK-1 and LIMK-2) related to human LIMK. LIMK-1 shares with human LIMK 95% of the total 647 amino acids and is probably a rat equivalent of human LIMK. LIMK-2 has an overall sequence and a domain structure similar to that of human LIMK and rat LIMK-1, but overall identity is 50-51% at the amino acid level. Like human LIMK, the protein kinase domains of rat LIMK-1 and -2 contain a characteristic sequence DLNSHN in subdomain VIB and a highly basic insert between subdomain VII and VIII. LIMK-1 and -2 are therefore closely related but distinct members of a novel LIM-containing protein kinase subfamily. Several forms of LIMK-2 transcripts encoding proteins that are N-terminally modified and/or C-terminally truncated are generated by alternative splicing or alternative initiation. Northern blot analysis revealed the expression of LIMK-1 mRNA predominantly in the brain and the expression of LIMK-2 mRNA in various tissues in the rat. Antibody raised against LIMK-1 specifically immunoprecipitated and identified in Rat2 fibroblast cells a 72 kDa protein, which has no detectable autophosphorylating activity but is capable of phosphorylating serine and threonine residues of myelin basic protein, by in vitro kinase reaction. As the LIMK family kinases have unique structural features, they are likely to have specific functions in previously uncharacterized signaling pathways.
Nunoue
K
K
Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan.
Ohashi
K
K
Okano
I
I
Mizuno
K
K
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000201:enzymology*; D002460:Cell Line; D016384:Consensus Sequence; D005347:Fibroblasts; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D012333:RNA, Messenger; D011494:Protein Kinases