Proschel, Christoph Johann Wolfgang; (1995) The cloning and characterisation of link1: A LIM-domain containing protein kinase. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis describes the isolation and cloning of a novel mouse gene, named mLimkl, which exhibits high homology to the human LIMK gene. mLimkl represents a single copy gene and maps to the distal end of mouse chromosome 5. Northern blot analysis showed preferential expression of a 3.5kb message in adult spinal cord and brain. In situ hybridisation studies confirmed high expression levels in the nervous system, particularly in the spinal cord and the cranial nerves and dorsal root ganglia. The amino acid sequence reveals two features which place mLimkl into a novel class of protein kinases. Firstly, although mLimkl contains all motifs found in catalytic kinase domains, amino acids previously described to be diagnostic of either serine/threonine- or tyrosine-kinases are not present. It is demonstrated that mLimkl-fusion protein can autophosphorylate on serine, tyrosine and threonine residues in vitro, and mutation of residue D460 within the IHRDL motif abolishes kinase activity. Secondly, mLimkl has two tandem LIM-domains in the amino-terminal region. These zinc-finger like domains can mediate protein-protein interactions and have been described in transcription factors and cytoskeletal proteins. The combination of LIM- and kinase domains may provide a novel route by which intracellular signaling can be integrated.

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