cAMP signaling caused activation of MLCP through regulation of RhoA/ROCK. Diagrammatic representation of the cross talk between cAMP and RhoA/ROCK signaling in platelets. Platelet activation leads to membrane relocalization and GTP loading of RhoA, which facilitates the activation of ROCK (1). A RhoA/ROCK/MYPT1 complex is formed leading to ROCK-dependent inhibitory phosphorylation of MLCP (2). Simultaneously, phospholipase C (PLC) is activated to generate inositol trisphosphate (IP3) and release intracellular Ca2+. The increased Ca2+ concentrations leads to the calmodulin (CAM) dependent activation of MCLK. Under these conditions, the ability of MLCP to dephosphorylate MLC is diminished (gray dotted line; upper panel). Activated PKA phosphorylates RhoA on ser¹⁸⁸, which prevents membrane relocalization and GTP loading. ROCK-mediated phosphorylation of MYPT1 is prevented, leaving MLCP in its active state. Here the dephosphorylation of MLC is the predominant pathway, while phosphorylation of MLC by MLCK is diminished (lower panel).