An Isoform of the Neuronal Cyclin-dependent Kinase 5 (Cdk5) Activator

摘要: Neuronal Cdc2-like kinase is a heterodimer of Cdk5 and 25-kDa subunit that derived from 35-kDa brain- neuron-specific protein called the neuronal activator (p35/p25nck5a) (Lew, J., Huang, Q.-Q., Qi, Z., Winkfein, R. Aebersold, R., Hunt, T., Wang, J. H. (1994) Nature 371, 423-426; Tsai, L. H., Delalle, I., Caviness, V. S., Jr., Chae, Harlow, E. 419-423). Upon screening human hippocampus library with bovien Nck5a cDNA, we uncovered distinct clone encoding 39-kDa isoform Nck5a. The isoform, designated (p39nck5ai), showed high degree sequence similarity to p35nck5a 57% amino acid identity. Northern blot analysis detected its mRNA transcript in bovine rat cerebrum cerebellum, but not any other tissues examined. In situ hybridization Nck5ai was enriched CA1 CA3 hippocampus, absent fimbria hippocampal formation. Among seven cell lines proliferating cultures, only PC12 N2A, two capable differentiating into neuron-like cells, were found contain mRNA. A 30-kDa truncated form expressed as glutathione S-transferase fusion Escherichia coli] associate an active kinase. Thus, shares many common characteristics p35nck5a, including Ckd5 activating activity expression. Both proteins show limited homology cyclins, suggesting they define new family cyclin-dependent kinase-activating proteins.