Biphasic Erk1/2 activation sequentially involving Gs and Gi signaling is required in beta3-adrenergic receptor-induced primary smooth muscle cell proliferation

► The beta-3 adrenergic receptor induces primary smooth muscle cell proliferation. ► Biphasic Erk1/2 activation, at 3 and 8 h, is required for proliferation. ► This biphasic activation depends upon distinct Gs/cAMP/PKA and Gi/Src/PI3K pathways. ► We identified a novel G-protein coupled receptor sequential signaling pathway.