Tau protein kinase II has a similar characteristic to cdc2 kinase for phosphorylating neurofilament proteins.

Tau protein kinase II purified from a bovine brain tau protein fraction (Ishiguro, K., Takamatsu, M., Tomizawa, K., Omori, A., Takahashi, M., Arioka, M., Uchida, T., and Imahori, K. (1992) J. Biol. Chem. 267, 10897-10901) was shown to have a similar substrate specificity to cdc2 kinase in that both phosphorylate neurofilament (NF) proteins. Tau protein kinase II recognized the dephosphorylated form of the heavy subunit of NF (NF-H) as a predominant substrate. The substrate was phosphorylated to the same extent with tau protein kinase II as with cdc2 kinase. Upon phosphorylation, the electrophoretic mobility of the NF-H on SDS-polyacrylamide gel electrophoresis changed to the position of the phosphorylated form. A synthetic peptide containing a KSPXK sequence was by far a better substrate for tau protein kinase II than that containing a KSPXX sequence, as was also observed with cdc2 kinase. NF-H lost its microtubule-associating ability upon phosphorylation with tau protein kinase II as well as with cdc2 kinase. Although anti-PSTAIR antibody (PSTAIR is an amino acid sequence commonly found in cdc2 and several cdc2-related kinases) failed to react with tau protein kinase II, tau protein kinase II bound to p13suc1-Sepharose beads (p13suc1 is a yeast protein known to bind to cdc2 kinase).