Overview:

The neuronal protein kinase, CDK5 is implicated in a vast array of normal neuronal functions including regulation of neurotransmitter synthesis (1), the presynaptic vesicle cycle (2), neurotransmitter receptor trafficking, and dopamine neurotransmission (3). CDK5 is active as a heterodimer with a 25 kDa protein. The 25 kDa protein is derived proteolytically from a 35 kDa brain and neuron-specific precursor protein (4). CDK5 phosphorylates a diverse list of substrates and has been implicated in a wide range of neurological and neuropsychiatric disorders, which include Alzheimer’s, Parkinson’s, Huntington’s, epilepsy, schizophrenia, and drug addiction (5).

References:

1. Kansy, J. et al. Identification of tyrosine hydroxylase as a physiological substrate of Cdk5. J. Neurochem. 2004 91, 374-384.

2. Nguyen, C. et al: Cdk5 and the mystery of synaptic vesicle endocytosis. J Cell Biol. 2003 163, 697- 699.

3. Bibb, J A. et al. Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signaling in neurons. Nature 1999 402, 669-671.

4. Tang, D. et al: Cyclin-dependent kinase 5 (Cdk5) and neuron-specific Cdk5 activators. Prog Cell Cycle Res. 1996;2:205-16.

5. Dhavan, R. et al: A decade of CDK5. Nat Rev Mol Cell Biol. 2001 Oct;2(10):749-59.