*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 10187789


    		J Biol Chem. 1999 Apr 9;274(15):10086-93.
     
			Inhibition of the Ca2+/calmodulin-dependent
			protein kinase I cascade by cAMP-dependent
			protein kinase.

			Matsushita M(1), Nairn AC.

			Author Information
			(1) Laboratory of Molecular and Cellular
			Neuroscience, The Rockefeller University,
			New York, New York 10021, USA.

			Several recent studies have shown that
			Ca2+/calmodulin-dependent protein kinase
			I (CaMKI) is phosphorylated and activated
			by a protein kinase (CaMKK) that is itself
			subject to regulation by Ca2+/calmodulin.
			In the present study, we demonstrate that
			this enzyme cascade is regulated by cAMP-mediated
			activation of cAMP-dependent protein kinase
			(PKA). In vitro, CaMKK is phosphorylated
			by PKA and this is associated with inhibition
			of enzyme activity. The major site of
			phosphorylation is threonine 108, although
			additional sites are phosphorylated with
			lower efficiency. In vitro, CaMKK is also
			phosphorylated by CaMKI at the same sites
			as PKA, suggesting that this regulatory
			phosphorylation might play a role as a
			negative-feedback mechanism. In intact PC12
			cells, activation of PKA with forskolin
			resulted in a rapid inhibition of both CaMKK
			and CaMKI activity. In hippocampal slices
			CaMKK was phosphorylated under basal conditions,
			and activation of PKA led to an increase
			in phosphorylation. Two-dimensional phosphopeptide
			mapping indicated that activation of PKA
			led to increased phosphorylation of multiple
			sites including threonine 108. These results
			indicate that in vitro and in intact cells
			the CaMKK/CaMKI cascade is subject to inhibition
			by PKA-mediated phosphorylation of CaMKK.
			The phosphorylation and inhibition of CaMKK
			by PKA is likely to be involved in modulating
			the balance between cAMP- and Ca2+-dependent
			signal transduction pathways.

			PMID: 10187789 [Indexed for MEDLINE]

     			                         Tweet       Print