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14‐3‐3 Proteins directly regulate Ca 2+ /calmodulin‐dependent protein kinase kinase α through phosphorylation‐dependent multisite binding
Author(s) -
Ichimura Tohru,
Taoka Masato,
Hozumi Yasukazu,
Goto Kaoru,
Tokumitsu Hiroshi
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.01.037
Subject(s) - protein kinase a , calmodulin , kinase , phosphorylation , microbiology and biotechnology , mitogen activated protein kinase kinase , mutant , chemistry , cyclin dependent kinase 9 , map2k7 , biochemistry , biology , cyclin dependent kinase 2 , enzyme , gene
Ca 2+ /calmodulin‐dependent protein kinase kinase α (CaMKKα) 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 CaMKKα 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 CaMKKα 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 CaMKKα.