Cyclin-dependent kinase 5

Cell division protein kinase 5 is an is_associated_with::enzyme that in humans is encoded by the CDK5 is_associated_with::gene. The protein encoded by this gene is part of the is_associated_with::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 is_associated_with::CDK5R1 or is_associated_with::CDK5R2. Unlike other cyclin dependent kinases, CDK5 does not also require is_associated_with::phosphorylation on the is_associated_with::T loop so that binding with the activator is sufficient to activate the kinase.

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

Experiments performed on mice lacking p35 (CDK5R1), 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 is_associated_with::synaptic vesicle is_associated_with::exocytosis via phosphorylation of is_associated_with::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.

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 is_associated_with::actin regulatory protein is_associated_with::caldesmon.

History
CDK5 was originally named NCLK (Neuronal CDC2-Like Kinase) 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 is_associated_with::T cell activation and play an important role in development of autoimmune disorders, such as is_associated_with::multiple sclerosis.

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