Figure 7. Schematic diagram of possible signaling pathways between RGS19, G proteins, cAMP/PKA cascades and transcription factors.

As a GAP, RGS19 terminates the action of active GTP-bound Gα_i, relieves the inhibition of adenylyl cyclase (AC) that produce cAMP. Elevation of intracellular cAMP level and the activation of PKA by agonists of G_s-coupled receptors, AC activator (forskolin) and cAMP analogues lead to phosphorylation of CREB, thus driving the expression of Nm23-H1/2. Endogenous or forskolin-induced Nm23-H1/2 protein expression can be suppressed by H-89 which inhibits PKA. Arrow with solid line, activation; blunted arrow, inhibition. CRE, cAMP responsive element; CREB, CRE-binding protein; P, phosphate; PKA, cAMP-dependent protein kinase.