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. 2001 Feb 20;98(5):2808–2813. doi: 10.1073/pnas.051634198

Figure 5.

Figure 5

Summary of depolarization-activated pathways to pCREB. (A) Superposed dynamics of 90 mM K+-induced pMAPK (▴) compared with the pure CaMK contribution to pCREB (○) and the MAPK contribution to pCREB (●). Values are normalized against the maximal changes of pCREB or pMAPK. Note that the peak in pMAPK significantly lags behind the peak of pCREB-CaMK. Interestingly, a single strong membrane depolarization induced a transient increase in pMAPK, in contrast to the slow-developing persistent pCREB contributed by the MAPK pathway. (B) Model demonstrating the confluence of different depolarization-activated, CaM-dependent processes converging on CREB Ser-133 in hippocampal pyramidal neurons. Rapid calmodulin translocation to the nucleus controls rapid CaMKIV-dependent CREB phosphorylation, slow CaMK-dependent MAPK signaling controls a late phase of CREB phosphorylation, and a calcineurin (CaN)-dependent phosphatase (PP1) pathway modulates CREB dephosphorylation. Together, these processes control the dynamics of CREB phosphorylation and the stimulus-evoked gene expression decision. Potential interactions between the CaMK and MAPK pathways include direct activation of the MAPK pathway by CaMKIV.