title: 14-3-3 Proteins directly regulate Ca(2+)/calmodulin-dependent protein kinase kinase alpha through phosphorylation-dependent multisite binding.
abstract: Ca(2+)/calmodulin-dependent protein kinase kinase alpha (CaMKKalpha) plays critical roles in the modulation of neuronal cell survival as well as many other cellular activities. Here we show that 14-3-3 proteins directly regulate CaMKKalpha when the enzyme is phosphorylated by protein kinase A on either Ser74 or Ser475. Mutational analysis revealed that these two serines are both functional: the CaMKKalpha mutant with a mutation at either of these residues, but not the double mutant, was inhibited significantly by 14-3-3. The mode of regulation described herein differs the recently described mode of 14-3-3 regulation of CaMKKalpha.
authors.affiliation: Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan. ichimura@nda.ac.jp
authors.forename: Tohru
authors.initials: T
authors.lastname: Ichimura
authors.forename: Masato
authors.initials: M
authors.lastname: Taoka
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Hozumi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tokumitsu
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism*; D002384:Catalysis / Q000187:drug effects; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013552:Swine
chemical_list: D048948:14-3-3 Proteins; D050505:Mutant Proteins; D010768:Phosphoserine; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase