In light of this evidence, together with recent studies demonstrating a pivotal role for PDE4 activity in regulating airway function in asthmatic individuals [19–21] and in animal models of allergic asthma [22–26], and that PDE4 activity is intrinsically increased in cultured human ASM (HASM) cells isolated from asthmatic individuals [27], the present study sought to determine whether asthmatic HASM cells exhibit constitutively increased PDE activity that is mechanistically attributed to intrinsically upregulated Gβγ signaling coupled to c-Src-induced activation of the Ras/MEK/ERK1/2 pathway. The gene discussed is MAPK3; the disease is allergic asthma.