Cyclin-dependent Kinase 5 - Physiological Role

Physiological Role

Recently Cdk5 has emerged as an essential kinase in sensory pathways. Recent reports of Pareek et al. from NIH suggest its necessity in pain signaling. CDK5 is required for proper development of the brain and to be activated, CDK5 must associate with CDK5R1 or CDK5R2. Unlike other cyclin dependent kinases, CDK5 does not also require phosphorylation on the T loop so that binding with the activator is sufficient to activate the kinase.

Cdk5 is involved in the processes of neuronal maturation and migration, phosphorylating the key intracellular adaptor of the reelin signaling chain.

Experiments performed on mice lacking p35, a necessary activator of cdk5 in early brain development, showed that the normal layering of neurons was reversed in the cortex. This disrupted lamination again implicated cdk5 in neuronal migration and plasticity.

Cdk5 is also involved in the regulation of synaptic vesicle exocytosis via phosphorylation of munc-18.

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