Protein kinase CK2 impairs spatial memory formation through differential cross talk with PI-3 kinase signaling: activation of Akt and inactivation of SGK1.

Casein kinase II (CK2) is a multifunctional serine/threonine protein kinase that is associated with the development of neuritogenesis and synaptic plasticity. The phosphoinositide 3-kinase (PI-3K)/Akt pathway is implicated in long-term memory formation. In addition, serum- and glucocorticoid-inducible kinase 1 (SGK1) is another downstream target of PI-3K signaling that was shown to play an important role in spatial memory formation. Whether CK2 may also affect memory formation and whether CK2 interacts with Akt and SGK1 during this process is unknown. In the present study, we found that water maze training significantly decreased CK2 activity in the rat hippocampal CA1 area but not in the dentate gyrus (DG) area. Transfection of the dominant negative mutant of CK2, CK2alphaA(156), to the CA1 area, but not to the DG area, decreased CK2 activity but enhanced spatial memory formation. Meanwhile, it increased SGK1 phosphorylation at Ser422, decreased Akt phosphorylation at Ser473, and increased cAMP response element-binding protein phosphorylation at Ser133. Transfection of the constitutively active SGK1, SGKS422D, enhanced whereas transfection of the wild-type Akt impaired spatial memory formation. Also, administration of the protein phosphatase 2A inhibitor, fostriecin, reversed the memory-impairing effect of CK2alphaWT. It also reversed the effect of CK2alphaWT in decreasing SGK1 phosphorylation. Akt Ser473 phosphorylation was moderately increased by CK2alphaWT and fostriecin treatment, but AktS473A mutant transfection reversed the memory-impairing effect of CK2alphaWT. These results together suggest that CK2 impairs spatial memory formation through differential cross talk with PI-3 kinase signaling by activation of Akt and inactivation of SGK1 through protein phosphatase 2A.