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.
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.
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 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 T cell activation and play an important role in development of autoimmune disorders, such as multiple sclerosis.
^Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999). "Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration". Nature402 (6762): 615–22. doi:10.1038/45159. PMID10604467.
^Kobayashi S, Ishiguro K, Omori A, Takamatsu M, Arioka M, Imahori K, Uchida T. (1993). "A cdc2-related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau protein kinase II, a proline-directed protein kinase associated with microtubule". FEBS Letters335 (2): 171–175. doi:10.1016/0014-5793(93)80723-8. PMID8253190.
^Kesavapany, Sashi; Lau Kwok-Fai; Ackerley Steven; Banner Steven J; Shemilt Stephen J A; Cooper Jonathan D; Leigh P Nigel; Shaw Christopher E; McLoughlin Declan M; Miller Christopher C J (June 2003). "Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". J. Neurosci. (United States) 23 (12): 4975–83. PMID12832520.
^Chen, F; Studzinski G P (June 2001). "Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation". Blood (United States) 97 (12): 3763–7. doi:10.1182/blood.V97.12.3763. ISSN0006-4971. PMID11389014.
Morishima-Kawashima M, Hasegawa M, Takio K et al. (1995). "Hyperphosphorylation of tau in PHF". Neurobiol. Aging16 (3): 365–71; discussion 371–80. doi:10.1016/0197-4580(95)00027-C. PMID7566346.CS1 maint: Explicit use of et al. (link)
Peruzzi F, Gordon J, Darbinian N, Amini S (2003). "Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway". J. Neurovirol. 8 Suppl 2 (2): 91–6. doi:10.1080/13550280290167885. PMID12491158.