cAMP enhances CSF-1-induced ERK activity and c-fos mRNA expression via a MEK-dependent and Ras-independent mechanism in macrophages

Abstract

Inhibition of MAPK by elevated intracellular cAMP has often been correlated with suppression of growth factor-induced proliferation. However, in murine bone marrow-derived macrophages (BMM) we show that the cAMP analogue, 8-bromo cAMP (8BrcAMP) (1 mM), despite being a dramatic G1 phase proliferation inhibitor, increased ERK activity both in the absence and presence of CSF-1; these increases were blocked by PD98059 (100 μM) suggesting MEK dependence. In contrast, CSF-1-stimulated p21(Ras) activity was blocked by 8BrcAMP thus correlating with the inhibition of proliferation. This is the first report to indicate that elevated intracellular cAMP can activate ERK activity while inhibiting prolife..