PubMed Journals: EMBO J

  Source:		PMID: 7641687

    		EMBO J. 1995 Aug 1;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.

			Haribabu B(1), Hook SS, Selbert MA, Goldstein
			EG, Tomhave ED, Edelman AM, Snyderman R,
			Means AR.

			Author Information
			(1) Department of Pharmacology, Duke University
			Medical Center, Durham, NC 27710, USA.

			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

			PMCID: PMC394442 PMID: 7641687 [Indexed
			for MEDLINE]

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