Ras is selectively involved in the late phase of CREB phosphorylation.
(A) Hippocampal pyramidal neurons from cultures 7 days
in vitro were cotransfected with dominant-negative Ras
(RasN17) and EGFP, then stimulated and fixed for immunocytochemistry
24 h later. pCREB staining is represented by red, EGFP marking the
transfected cells is represented by green, and in the merged image, the
conjunction of red and green appears as yellow. Note the robust CREB
phosphorylation (yellow nucleus in the merged image) at the early time
point (90 mM K+ 3′) and the selectively reduced CREB
phosphorylation at the late time point (wash 30′) in the transfected
cells. MAP2 staining was used to identify all of the neurons; this is
shown at the right in white. (B) Summary data are
graphed below the representative examples. Dominant-negative Ras had no
effect at the early time point (P > 0.2), but
produced a partial inhibition at the late time point
(P < 0.01), demonstrating that the MAPK pathway is
selectively involved in the late phase but not the early phase of
depolarization-induced CREB phosphorylation, consistent with the
PD98059 results. Values are mean ± 1 SEM, n
> 50 neurons for each condition.