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 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.
Guidato
S
S
Department of Clinical Neurosciences, Institute of Psychiatry, London, England.
McLoughlin
D M
DM
Grierson
A J
AJ
Miller
C C
CC
D000818:Animals; D019556:COS Cells / Q000378:metabolism; D056742:Cyclin D2; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000502:physiology*; D004347:Drug Interactions; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D014162:Transfection
C080336:CCND2 protein, human; C486197:Ccnd2 protein, rat; D056742:Cyclin D2; D016213:Cyclins; D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C495905:CDK5 protein, human; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases