Multiple Ca super(2+)-calmodulin-dependent protein kinase kinases from rat brain: Purification, regulation by Ca super(2+)-calmodulin, and partial amino acid sequence

• Published in: The Journal of biological chemistry 1996-01, Vol.271 (18), p.10806-10810
• Main Authors: Edelman, A M, Mitchelhill, KI, Selbert, MA, Anderson, KA, Hook, S S, Stapleton, D, Goldstein, E G, Means, A R, Kemp, B E
• Format: Article
• Language: English
• Subjects: Caenorhabditis elegans
• ISSN: 0021-9258

We have purified to near homogeneity from rat brain two Ca super(2+)-calmodulin-dependent protein kinase I (CaM kinase I) activating kinases, termed here CaM kinase I kinase- alpha and CaM kinase I kinase- beta (CaMKIK alpha and CaMKIK beta respectively). Both CaMKIK alpha and CaMKIK beta are also capable of activating CaM kinase IV. Activation of CaM kinase I and CaM kinase IV occurs via phosphorylation of an equivalent Thr residue within the "activation loop" region of both kinases, Thr-177 and Thr-196, respectively. The activities of CaMKIK alpha and CaMKIK beta are themselves strongly stimulated by the presence of Ca super(2+)-CaM, and both appear to be capable of Ca super(2+)-CaM-dependent autophosphorylation. Automated microsequence analysis of the purified enzymes established that CaMKIK alpha and - beta are the products of distinct genes. In addition to rat, homologous nucleic acids corresponding to these CaM kinase kinases are present in humans and the nematode, Caenorhabditis elegans. CaMKIK alpha and CaMKIK beta are thus representatives of a family of enzymes, which may function as key intermediaries in Ca super(2+)-CaM-driven signal transduction cascades in a wide variety of eukaryotic organisms.