NEUROFILAMENTS ARE PART OF THE HIGH-MOLECULAR-WEIGHT COMPLEX CONTAINING NEURONAL CDC2-LIKE KINASE (NCLK)

A cdc2-like kinase (nclk, comprised of cdk5 and its activator p25(nck5 a)) that localizes primarily to neuronal cells has,recently been ident ified. Although its precise physiological role remains unclear, a vari ety of nuclear and cytoplasmic proteins that may-be targets for phosph orylation by this kinase have been suggested in various developmental and pathological states. Here we provide evidence for a functional ass ociation between nclk and neurofilament proteins: (i) brain neurofilam ent preparations include cdk5 and p25(nck5a); (ii) nclk copurifies wit h neurofilament proteins using Mono-S and gel-filtration column chroma tographic procedures; (iii) neurofilaments are coprecipitated with cdk 5 kinase; and (iv) the addition of radiolabeled ATP to the immunopreci pitated complex results in phosphorylation of the cytoskeletal protein . These results are consistent with the formation of a functional macr omolecular complex between nclk and neurofilaments in vivo and suggest a possible role for this kinase in regulating neuronal cytoskeletal n etworks. (C) 1997 Elsevier Science B.V.