Schematic illustrating how growth factors such as CSF-1 and IL-3 may cooperate with cAMP/PKA to activate the ERK/p90^rsk pathway in myeloid progenitors. CSF-1 stimulates the activities of both Raf-1 and ERK in 32D cells. In the presence of cAMP, Raf-1 activation is prevented yet ERK activity is enhanced. The simplest explanation is that CSF-1 uses an alternate (not Raf-1) cAMP-insensitive kinase as the MAPKKK. Activation of MAPKKK is likely to be Ras-dependent, because expression of oncogenic Ras together with elevations in cAMP levels can recapitulate the synergistic stimulation of ERK by CSF-1 and cAMP. Whether cAMP can itself activate MAPKKK is not clear (see text). Instead, the dominant stimulatory effect of cAMP appears to be at a step after MEK1 activation, because MEK1 activity itself is not enhanced in the presence of cAMP but is required for the synergistic action of cAMP. Inhibition of the MEK-ERK pathway results in a significant but incomplete suppression of cell proliferation, indicating that growth factors such as CSF-1 and IL-3 activate other pathways required for optimal proliferation and survival in myeloid progenitor cell lines. These pathways could be mediated by both Ras-independent (depicted by pathways emanating from the receptor) and -dependent (depicted by pathways emanating from Ras) mechanisms and both are potentially targets for cAMP action. cAMP and PKA can also presumably influence pathways in the cell not directly activated by CSF-1 or IL-3 (depicted by an arrow emanating from PKA not targeted at a receptor-activated pathway).