Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 14 (15), 3679-86

Human Calcium-Calmodulin Dependent Protein Kinase I: cDNA Cloning, Domain Structure and Activation by Phosphorylation at threonine-177 by Calcium-Calmodulin Dependent Protein Kinase I Kinase

Affiliations

Human Calcium-Calmodulin Dependent Protein Kinase I: cDNA Cloning, Domain Structure and Activation by Phosphorylation at threonine-177 by Calcium-Calmodulin Dependent Protein Kinase I Kinase

B Haribabu et al. EMBO J.

Abstract

Human Ca(2+)-calmodulin (CaM) dependent protein kinase I (CaMKI) encodes a 370 amino acid protein with a calculated M(r) of 41,337. The 1.5 kb CaMKI mRNA is expressed in many different human tissues and is the product of a single gene located on human chromosome 3. CaMKI 1-306, was unable to bind Ca(2+)-CaM and was completely inactive thereby defining an essential component of the CaM-binding domain to residues C-terminal to 306. CaMKI 1-294 did not bind CaM but was fully active in the absence of Ca(2+)-CaM, indicating that residues 295-306 are sufficient to maintain CaMKI in an auto-inhibited state. CaMKI was phosphorylated on Thr177 and its activity enhanced approximately 25-fold by CaMKI kinase in a Ca(2+)-CaM dependent manner. Replacement of Thr177 with Ala or Asp prevented both phosphorylation and activation by CaMKI kinase and the latter replacement also led to partial activation in the absence of CaMKI kinase. Whereas CaMKI 1-306 was unresponsive to CaMKI kinase, the 1-294 mutant was phosphorylated and activated by CaMKI kinase in both the presence and absence of Ca(2+)-CaM although at a faster rate in its presence. These results indicate that the auto-inhibitory domain in CaMKI gates, in a Ca(2+)-CaM dependent fashion, accessibility of both substrates to the substrate binding cleft and CaMKI kinase to Thr177. Additionally, CaMKI kinase responds directly to Ca(2+)-CaM with increased activity.

Similar articles

See all similar articles

Cited by 39 PubMed Central articles

See all "Cited by" articles

References

    1. Anal Biochem. 1977 Dec;83(2):346-56 - PubMed
    1. J Biol Chem. 1992 Jul 5;267(19):13460-5 - PubMed
    1. J Biol Chem. 1985 Nov 25;260(27):14471-6 - PubMed
    1. J Biol Chem. 1987 May 25;262(15):7273-81 - PubMed
    1. FEBS Lett. 1987 Jul 13;219(1):259-63 - PubMed

Publication types

MeSH terms

Associated data

LinkOut - more resources

Feedback