Dm. Tang et al., AN ISOFORM OF THE NEURONAL CYCLIN-DEPENDENT KINASE-5 (CDK5) ACTIVATOR, The Journal of biological chemistry, 270(45), 1995, pp. 26897-26903
Neuronal Cdc2-like kinase is a heterodimer of Cdk5 and a 25-kDa subuni
t that is derived from a 35-kDa brain- and neuron-specific protein cal
led the neuronal Cdk5 activator (p35/p25(nck5a)) (Lew, J., Huang, Q.-Q
., Qi, Z., Winkfein, R. J., Aebersold, R., Hunt, T., and Wang, J. H. (
1994) Nature 371, 423-426; Tsai, L. H., Delalle, I., Caviness, V. S.,
Jr., Chae, T., and Harlow, E. (1994) Nature 371, 419-423). Upon screen
ing of a human hippocampus library with a bovine Nck5a cDNA, we uncove
red a distinct clone encoding a 39-kDa isoform of Nck5a. The isoform,
designated the neuronal Cdk5 activator isoform (p39(nck5ai)), showed a
high degree of sequence similarity to p35(nck5a) with 57% amino acid
identity. Northern blot analysis detected its mRNA transcript in bovin
e and rat cerebrum and cerebellum, but not in any other rat tissues ex
amined. In situ hybridization showed that Nck5ai was enriched in CA1 t
o CA3 of the hippocampus, but absent in the fimbria of hippocampal for
mation. Among seven cell lines in proliferating cultures, only PC12 an
d N2A, two cell lines capable of differentiating into neuron-like cell
s, were found to contain Nck5ai mRNA. A 30-kDa truncated form of Nck5a
i expressed as a glutathione S-transferase fusion protein in Escherich
ia coli] was found to associate with Cdk5 to form an active Cdk5 kinas
e. Thus, the isoform shares many common characteristics with p35(nck5a
), including Ckd5 activating activity and brain- and neuron-specific e
xpression. Both proteins show limited sequence homology to cyclins, su
ggesting that they define a new family of cyclin-dependent kinase-acti
vating proteins.