Tyrosine phosphorylation and activation of mitogen-activated protein kinase in the rat brain following transient cerebral ischemia.

Activation of trophic factor receptors stimulates tyrosine phosphorylation on proteins and supports neuronal survival. We report that in the recovery phase following reversible cerebral ischemia, tyrosine phosphorylation increases in the membrane fraction of the resistant hippocampal CA3/dentate gyrus (DG) region, whereas in the sensitive CA1 region or striatum, tyrosine phosphorylation is less marked or decreases. In the cytosolic fractions, a 42-kDa protein, identified as mitogen-activated protein (MAP) kinase, is markedly phosphorylated and activated immediately following ischemia, in particular in CA3/DG, but not in striatum. In the CA1 region, phosphorylation of MAP kinase is less intense and decreases later during reperfusion, which could explain the delay of neuronal degeneration in this structure. The data suggest that in ischemia-resistant neurons the growth factor receptor-coupled signaling cascade is stimulated and, through its effects on DNA transcription and mRNA translation, supports neuronal survival.