REGION-SPECIFIC TARGETS OF P42 P44(MAPK) SIGNALING IN RAT-BRAIN/

In vitro studies indicate that p42/p44(MAPK) phosphorylate both nuclea r and cytoplasmic proteins. However, the functional targets of p42/p44 (MAPK) activation in vivo remain unclear. To address this question, we localized activated p42/p44(MAPK) in hippocampus and cortex and deter mined their signaling effects after electroconvulsive shock treatment (ECT) in rats. Phosphorylated p42/p44(MAPK) content increased in the c ytoplasm of hippocampal neurons in response to ECT. Consistent with th is cytoplasmic localization, inhibition of ECT-induced p42/p44(MAPK) a ctivation by the extracellular signal-regulated kinase kinase inhibito r PD098059 blocked phosphorylation of the cytoplasmic protein microtub ule-associated protein 2c (MAP2c), but failed to inhibit the induction of the nuclear protein c-Fos in response to ECT. In contrast to hippo campal neurons, cortical neurons exhibited an increase in amount of ph osphorylated p42/p44(MAPK) in both the nucleus and cytoplasm after ECT . Accordingly, PD098059 blocked the induction of Fos-like immunoreacti vity in the nuclei of cortical neurons as well as MAP2c phosphorylatio n in the cytoplasm. Our data indicate that both nuclear and cytoplasmi c substrates can be activated by p42/p44(MAPK) in vivo. However, the f unctional targets of p42/p44(MAPK) signaling depend on the precise loc ation of p42/p44(MAPK) within different subcellular compartments of br ain regions, These results indicate unique functional pathways of p42/ p44(MAPK)-mediated signal transduction within different brain regions in vivo.