Region-specific targets of p42/p44MAPK signaling in rat brain.
J Neurochem
; 70(2): 558-71, 1998 Feb.
Article
in En
| MEDLINE
| ID: mdl-9453550
ABSTRACT
In vitro studies indicate that p42/p44MAPK phosphorylate both nuclear and cytoplasmic proteins. However, the functional targets of p42/p44MAPK activation in vivo remain unclear. To address this question, we localized activated p42/p44MAPK in hippocampus and cortex and determined their signaling effects after electroconvulsive shock treatment (ECT) in rats. Phosphorylated p42/p44MAPK content increased in the cytoplasm of hippocampal neurons in response to ECT. Consistent with this cytoplasmic localization, inhibition of ECT-induced p42/p44MAPK activation by the extracellular signal-regulated kinase kinase inhibitor PD098059 blocked phosphorylation of the cytoplasmic protein microtubule-associated protein 2c (MAP2c), but failed to inhibit the induction of the nuclear protein c-Fos in response to ECT. In contrast to hippocampal neurons, cortical neurons exhibited an increase in amount of phosphorylated p42/p44MAPK in both the nucleus and cytoplasm after ECT. Accordingly, PD098059 blocked the induction of Fos-like immunoreactivity in the nuclei of cortical neurons as well as MAP2c phosphorylation in the cytoplasm. Our data indicate that both nuclear and cytoplasmic substrates can be activated by p42/p44MAPK in vivo. However, the functional targets of p42/p44MAPK signaling depend on the precise location of p42/p44MAPK within different subcellular compartments of brain regions. These results indicate unique functional pathways of p42/p44MAPK-mediated signal transduction within different brain regions in vivo.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Signal Transduction
/
Calcium-Calmodulin-Dependent Protein Kinases
/
Mitogen-Activated Protein Kinase 1
/
Mitogen-Activated Protein Kinase Kinases
/
Mitogen-Activated Protein Kinases
Limits:
Animals
Language:
En
Journal:
J Neurochem
Year:
1998
Document type:
Article
Affiliation country:
United States