Mutual protection of microtubule-associated protein 2 (MAP2) and cyclic AMP-dependent protein kinase II against μ-calpain

Abstract

Phosphorylation by adenosine-3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA), but not by Ca++-calmodulin-dependent protein kinase II (CaMK II), was shown earlier to protect microtubule-associated protein 2 (MAP2) from cleavage by m-calpain (Johnson and Foley: J Neurosci Res 34: 642- 647, 1993). We reinvestigated this phenomenon with the physiologically more relevant μ-calpain and found a qualitatively similar but quantitatively different picture. We further demonstrate that 1) protection is biphasically dependent on the degree of phosphorylation; 2) Ca++-phospholipid-dependent protein kinase (PKC) has about the same effect as PKA; 3) the effects of kinases A and C are not additive; and 4) stripping of native MAP2 from its phosphate content (17.8 ± 2.3 mol/mol) enhances calpain-olysis 3.6-fold. A reciprocal effect between kinase A and MAP2 was found: the RII, but not the RI, regulatory subunit of kinase A, which was shown to bind specifically to MAP2, is protected by MAP2 from μ-calpain attack. It is suggested that the specific anchoring of kinase A-II on MAP2 may serve not only kinase targeting in the dendrites, but also protection from calpainolytic degradation.