LIMK1 IS PREDOMINANTLY EXPRESSED IN NEURAL TISSUES AND PHOSPHORYLATESSERINE, THREONINE AND TYROSINE RESIDUES IN-VITRO

We have isolated the murine Limk1 gene, which is a single copy gene lo cated at the distal end of mouse chromosome 5. Limk1 exhibits a 95% ho mology to the human homologue, LIMK, which contains two LIM domains an d a putative protein kinase domain. Although Limk1 and LIMK contain al l motifs found in catalytic kinase domains, amino acids previously des cribed to be diagnostic of either serine/threonine- or tyrosine-kinase s are not present. It is demonstrated that GST-Limk1-fusion protein ca n autophosphorylate on serine, tyrosine and threonine residues in vitr o and that mutation of residue D460 within the IHRDL motif abolishes k inase activity. Northern blot showed preferential expression of a 3.5 kb message in adult spinal cord and brain. In situ hybridisation confi rmed high expression levels in the nervous system, particularly in the spinal cord and the cranial nerve and dorsal root ganglia. Limk1 also contains two tandem LIM-domains. These zinc-finger like domains can m ediate protein-protein interactions and have been described in nuclear and cytoskeletal proteins. The combination of LIM- and kinase domains may provide a novel route by which intracellular signalling can be in tegrated.