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The Journal of Neuroscience, June 1, 1999, 19(11):4337-4348
The Mitogen-Activated Protein Kinase Cascade Couples PKA and PKC
to cAMP Response Element Binding Protein Phosphorylation in Area CA1 of
Hippocampus
Erik D.
Roberson ,
Joey D.
English ,
J. Paige
Adams ,
Joel
C.
Selcher ,
Christine
Kondratick, and
J. David
Sweatt
Division of Neuroscience, Baylor College of Medicine, Houston,
Texas 77030
Activation of the mitogen-activated protein kinase (MAPK) cascade
recently was discovered to play an important role in synaptic plasticity in area CA1 of rat hippocampus. However, the upstream mechanisms regulating MAPK activity and the downstream effectors of
MAPK in the hippocampus are uncharacterized. In the present studies we
observed that hippocampal MAPK activation is regulated by both the PKA
and PKC systems; moreover, we found that a wide variety of
neuromodulatory neurotransmitter receptors (metabotropic glutamate
receptors, muscarinic acetylcholine receptors, dopamine receptors, and
 -adrenergic receptors) couple to MAPK activation via these two
cascades. In additional studies we observed that PKC is a powerful
regulator of CREB phosphorylation in area CA1. MAPK plays a critical
role in transcriptional regulation by PKC, because MAPK activation is a
necessary component for increased CREB phosphorylation in response to
the activation of this kinase. Surprisingly, we also observed that MAPK
activation is necessary for PKA coupling to CREB phosphorylation in
area CA1. Overall, these studies indicate an unexpected richness of
diversity in the regulation of MAPK in the hippocampus and suggest the
possibility of a broad role for the MAPK cascade in regulating gene
expression in long-term forms of hippocampal synaptic plasticity.
Key words:
MAPK; PKA; PKC; CREB; hippocampus; LTP; learning and
memory
Copyright © 1999 Society for Neuroscience 0270-6474/99/19114337-12$05.00/0
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