Cyclin-dependent kinase 5


Cell division protein kinase 5 is an enzyme that in humans is encoded by the CDK5 gene. The protein encoded by this gene is part of the cyclin-dependent kinase family.

Physiological role

Recently Cdk5 has emerged as an essential kinase in sensory pathways. Recent reports of Pareek et al. 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.
Blocking Cdk5 in mice helps them get over fear learned in a particular context. Conversely, the learned fear persisted when the enzyme's activity was increased in the hippocampus, the brain's centre for storing memories.
Cdk5 has also been shown to play an intimate role in the pathogenesis of addiction.

Role in disease

Dysregulation of this enzyme has been implicated in several neurodegenerative diseases including Alzheimer's.
It is involved in invasive cancers, apparently by reducing the activity of the actin regulatory protein caldesmon.

History

CDK5 was originally named NCLK due to its similar phosphorylation motif. CDK5 in combination with an activator was also referred to as Tau Protein Kinase II. Furthermore, Cdk5 has been reported to be involved in T cell activation and play an important role in development of autoimmune disorders, such as multiple sclerosis.

Interactive pathway map

Interactions

Cyclin-dependent kinase 5 has been shown to interact with LMTK2, NDEL1, CDK5R1, Nestin and PAK1.