CYCLIN D2 INTERACTS WITH CDK-5 AND MODULATES CELLULAR CDK-5 P35 ACTIVITY/

Cyclin-dependent kinase-5 (cdk-5) is a serine/threonine kinase that di splays neurone-specific activity. Experimental manipulation of cdk-5 e xpression in neurones has shown that cdk-5 is essential for proper dev elopment of the nervous system and, in particular, for out growth of n eurites. Such observations suggest that cdk-5 activity must be tightly controlled during development of the nervous system. To identify poss ible regulators of cdk-5, we used the yeast two-hybrid system to searc h for proteins that interact with cdk-5. In two independent yeast tran sformation events, cyclin D2 interacted with cdk-5. Immunoprecipitatio n experiments confirmed that cyclin D2 and cdk-5 interact in mammalian cells. Cyclin D2 did not activate cdk-5 as assayed using three differ ent substrates, which was in contrast to a known cdk-5 activator, p35. However, cyclin D2 expression led to a decrease in cdk-5/p35 activity in transfected cells. As cyclin D2 and cdk-5 are known to share overl apping patterns of expression during development of the CNS, the resul ts presented here suggest a role for cyclin D2 in modulating cdk-5 act ivity in postmitotic developing neurones.