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Abstract
Hormonal stimulation of cyclic adenosine monophosphate (cAMP) and the cAMP-dependent
protein kinase PKA regulates cell growth by multiple mechanisms. A hallmark of cAMP
is its ability to stimulate cell growth in many cell types while inhibiting cell growth
in others. In this review, the cell type-specific effects of cAMP on the mitogen-activated
protein (MAP) kinase (also called extracellular signal-regulated kinase, or ERK) cascade
and cell proliferation are examined. Two basic themes are discussed. First, the capacity
of cAMP for either positive or negative regulation of the ERK cascade accounts for
many of the cell type-specific actions of cAMP on cell proliferation. Second, there
are several specific mechanisms involved in the inhibition or activation of ERKs by
cAMP. Emerging new data suggest that one of these mechanisms might involve the activation
of the GTPase Rap1, which can activate or inhibit ERK signaling in a cell-specific
manner.