Cyclin D2 Interacts with cdk‐5 and Modulates Cellular cdk‐5/p35 Activity

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Abstract
Cyclin‐dependent kinase‐5 (cdk‐5) is a serine/threonine kinase that displays neurone‐specific activity. Experimental manipulation of cdk‐5 expression in neurones has shown that cdk‐5 is essential for proper development of the nervous system and, in particular, for outgrowth of neurites. Such observations suggest that cdk‐5 activity must be tightly controlled during development of the nervous system. To identify possible regulators of cdk‐5, we used the yeast two‐hybrid system to search for proteins that interact with cdk‐5. In two independent yeast transformation events, cyclin D2 interacted with cdk‐5. Immunoprecipitation experiments confirmed that cyclin D2 and cdk‐5 interact in mammalian cells. Cyclin D2 did not activate cdk‐5 as assayed using three different 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 overlapping patterns of expression during development of the CNS, the results presented here suggest a role for cyclin D2 in modulating cdk‐5 activity in postmitotic developing neurones.

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