Cdk5/p25, active

Cyclin-dependent Kinase 5 (cdk5) is a cyclin-dependent serine/threonine kinase that, while not involved in cell proliferation, plays a critical role in neuron development. The kinase is activated strongly when it complexes with neuron-specific activators, especially p35, but less strongly when it complexes with cyclins. In contrast, a constitutively active form of the complex results when cdk5 binds with p25 or p21 (truncated forms of p35). The cdk5/p35 complex has been implicated in neurite outgrowth, neuronal differentiation and neuronal migration and axon patterning. The complex phosphorylates the tau protein at Ser199, Ser202 and Thr205. Hyperphosphorylated tau will cause neurofibrillary tangles and lead to Alzheimer's disease. Research has also shown the cdk5/p35 complex is associated with drug addiction and amyotrophic lateral sclerosis. Inhibitors may prevent the progression of Alzheimer’s disease, amyotrophic lateral sclerosis, and other neurodegenerative diseases. GenBank X66364 / p25 is an in vivo cleavage product of the p35 protein described inGenBank X80343. The recombinant product contains the full length p25 protein, equivalent to residues F98–end of p35, as described in Gentry et al., Nature 402, 615-622, 1999.