REGULATORY PROPERTIES OF NEURONAL CDC2-LIKE KINASE

Neuronal cdc2-like kinase, nclk, is a heterodimer of cyclin dependent protein kinase 5, cdk5, and a 25 kDa subunit derived from a novel, neu ron-specific, 35 kDa protein: p35. The characterization and regulation of nclk will be summarized in this minireview. The activity of nclk a ppears to be governed by highly complex regulatory mechanisms includin g protein-protein interaction, protein phosphorylation and isoforms. T he histone H1 kinase activity of nclk is absolutely dependent of the i nteraction between the 25 kDa subunit and the catalytic subunit, cdk5. In addition, nclk interacts with other cellular proteins to form macr omolecular complexes. The kinase activity of nclk is inhibited in vitr o by the phosphorylation reactions of a weel-like protein tyrosine kin ase and a protein serine/threonine kinase from bovine thymus. Northern blot analysis has revealed the existence of two populations of p35 mR NA of 2 and 4 kb. A novel cDNA encoding a p35 homologous protein has b een obtained from a human hippocampus library.