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)-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 mu-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 calpainolysis 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 mu-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.
Alexa
A
A
Institute of Enzymology, Hungarian Academy of Sciences, Budapest, Hungary.
Tompa
P
P
Baki
A
A
Vereb
G
G
Friedrich
P
P
D000818:Animals; D002154:Calpain / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D008869:Microtubule-Associated Proteins; D000242:Cyclic AMP; D011494:Protein Kinases; D002154:Calpain