STRUCTURE, FUNCTION, AND REGULATION OF NEURONAL CDC2-LIKE PROTEIN-KINASE

We have identified and purified from bovine brain a novel protein kina se which catalyzes in vitro phosphorylation of neurofilament proteins NF-H and NF-M and tau proteins at sites implicating the enzyme in the regulation of neurocytoskeleton dynamics and in Alzheimer pathology. T he protein kinase displays a phosphorylation site specificity similar or identical to the cell cycle regulatory kinase, cdc2 kinase. The pur ified kinase is a heterodimer of a cdc2-like catalytic subunit, called cdk5, and a 25 kDa regulatory subunit. The regulatory subunit is esse ntial for kinase activity, and it is derived from a 35 kDa protein, p3 5 by proteolysis. Northern blot analysis of tissue distribution indica tes that cdk5 is widely distributed but especially rich in brain, wher eas p35 expression is only found in brain. The protein kinase is there fore termed neuronal cdc2-like kinase. The neuron-specificity of the e nzyme appears to be conferred by the regulatory subunit. During cell d ivision, cdc2 kinase is regulated by complex phosphorylation mechanism s involving a network of specific protein kinases. Some of these kinas es or their homologs have been found in mammalian brains and they may be involved in the regulation of neuronal cdc2-like kinase.