MUTUAL PROTECTION OF MICROTUBULE-ASSOCIATED PROTEIN-2 (MAP2) AND CYCLIC-AMP-DEPENDENT PROTEIN-KINASE-II AGAINST MU-CALPAIN

Phosphorylation by adenosine-3',5'-cyclic monophosphate (cAMP)-depende nt protein kinase (PKA), but not by Ca++-calmodulin-dependent protein kinase II (CaMK II), was shown earlier to protect microtubule-associat ed protein 2 (MAP2) from cleavage by m-calpain (Johnson and Foley: J N eurosci Res 34: 642-647, 1993). We reinvestigated this phenomenon with the physiologically more relevant mu-calpain and found a qualitativel y similar but quantitatively different picture. We further demonstrate that 1) protection is biphasically dependent on the degree of phospho rylation; 2) Ca++-phospholipid-dependent protein kinase (PKC) has abou t the same effect as PKA; 3) the effects of kinases A and C are not ad ditive; and 4) stripping of native MAP2 from its phosphate content (17 .8 +/- 2.3 mol/mol) enhances calpainolysis 3.6-fold. A reciprocal effe ct between kinase A and MAP2 was found: the RII, but not the RI, regul atory subunit of kinase A, which was shown to bind specifically to MAP 2, is protected by MAP2: from mu-calpain attack. It is suggested that the specific anchoring of kinase A-II on MAP2 may serve not only kinas e targeting in the dendrites, but also protection from calpainolytic d egradation. (C) 1996 Wiley-Liss, Inc.