Figure 8.

Model of cAMP action on Rho to induce dendrite outgrowth and melanogenesis in B16 melanoma cells. According to our results we propose a model to explain possible mechanisms of cAMP-induced differentiation in the melanocyte cell system. Up-regulation of the cAMP pathway by α-MSH binding to its receptor or by cAMP-elevating agents would lead to the sequential inactivation of PI3-K, Rac, Rho, and its target P160^ROCK. Inhibition of P160^ROCK results in MLCK inactivation. Inactive MLCK does not phosphorylate MLC, thus impairing myosin binding to actin and preventing actin bundling in stress fibers. The retraction of stress fibers would lead to other cellular events, depending on the microtubular network, to promote the final dendrite outgrowth in B16 melanoma cells. At the same time, inactive Rho would cooperate with other molecular mechanisms in the induction of tyrosinase expression leading to melanogenesis. AC, adenylyl cyclase; FK, forskolin; PKA, protein kinase A; PI3-K, phosphatidylinositol 3-kinase; MLCK, myosin light chain kinase.