Multiple Ca-Calmodulin-dependent Protein Kinase Kinases from Rat Brain

• Published in: The Journal of biological chemistry Vol. 271; no. 18; p. 10806
• Main Authors: Arthur M. Edelman, Ken I. Mitchelhill, Michele A. Selbert, Kristin A. Anderson, Sara S. Hook, David Stapleton, Elaine G. Goldstein, Anthony R. Means, Bruce E. Kemp
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 03-05-1996
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.18.10806

We have purified to near homogeneity from rat brain two Ca -calmodulin-dependent protein kinase I (CaM kinase I) activating kinases, termed here CaM kinase I kinase-α and CaM kinase
I kinase-β (CaMKIKα and CaMKIKβ, respectively). Both CaMKIKα and CaMKIKβ 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 CaMKIKα and CaMKIKβ are themselves strongly stimulated
by the presence of Ca -CaM, and both appear to be capable of Ca -CaM-dependent autophosphorylation. Automated microsequence analysis of the purified enzymes established that CaMKIKα and
-β 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 . CaMKIKα and CaMKIKβ are thus representatives of a family of enzymes, which may function as key intermediaries in Ca -CaM-driven signal transduction cascades in a wide variety of eukaryotic organisms.