PROTEIN SERINE THREONINE KINASES (PKA, PKC AND CAMKII) INVOLVED IN ISCHEMIC BRAIN PATHOLOGY/

The protein serine/threonine kinases which are highly expressed in the central nervous system (CNS) are severely affected by brain ischemia. Irrespective of substantial differences among the particular members of this group of kinases, their responses to ischemic stress show a lo t of similarities. Initially they are switched on by facilitated inter action with their specific activators/second messengers like cyclic AM P, 1,2,-sn-diacylglicerol and particularly Ca2+, then they are translo cated to highly specific regions of plasma membranes. After phosphoryl ation of target proteins, the kinases are deactivated by means of diff erent routes. Activity of PKA is regulated by its direct access to cAM P. In the case of CaMKII, it is probably achieved by its extensive, in hibitory autophosphorylations, while PKC seems to be proteolytically d egraded. These biphasic changes in serine/threonine kinases activity m ay play a critical role in the evolution of postischemic brain injury and provide a mechanism for a variety of short- and long-term signalli ng events.