| Protein kinase B ( PKB ) was recently reported to be activated on the phosphorylation of Thr ( 308 ) by Ca ( 2+ ) / calmodulin dependent protein kinase kinase alpha ( CaM kinase kinase alpha ) , suggesting that PKB was regulated through not only the phosphoinositide 3 kinase pathway but also the Ca ( 2+ ) / calmodulin protein kinase pathway . ^^^ The activation of PKB by CaM kinase kinase alpha was as high as 300 fold after incubation for 30 min under the phosphorylation conditions , and still increased thereafter , suggesting that the maximal activation of PKB on phosphorylation of the Thr ( 308 ) residue is several hundred fold . ^^^ On the other hand , the 5 ( max ) value of CaM kinase kinase alpha for the phosphorylation of PKB was more than two orders of magnitude lower than that for CaM kinase 4 , although the K ( m ) values for PKB and CaM kinase 4 were not significantly different , raising the question of whether or not PKB is a physiological substrate of CaM kinase kinase alpha . ^^^ Besides CaM kinase kinase alpha , CaM kinase 2 also remarkably activated PKB . ^^^ However , the specific activities of CaM kinase kinase alpha and CaM kinase 2 as to the activation of PKB were more than three orders of magnitude lower than that of 3 phosphoinositide dependent protein kinase 1 ( PDK 1 ) . . ^^^ |