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The small GTPases RhoA and Cdc42 regulate diverse aspects of cell morphogenesis and cell migration through various effector proteins.Effector kinases ROK and MRCK act downstream of RhoA and Cdc42 respectively,playing pivotal roles in regulating myosin II activity through their phosphorylation activity on the Regulatory Myosin Light Chain 2 (RMLC). Interestingly the activity of these two related kinases differs in their substrate specificity towards RMLC both in vitro and in vivo.MRCK specifically phosphorylates RMLC at S19 (monophosphorylation) whereas ROK at S19 as well as T18 and S19 (diphosphorylation) and these can be easily detected with specific antibodies.Together with specific inhibitors,such differences offer a good prediction of kinases involved in various cellular compartments in cultured cells.Hence di-phosphorylation of RMLC on myosin associated with actin stress fibers by Rho kinase ROK is highly sensitive to inhibitor Y-27632 whereas lamellar actomyosin bundles (mostly S19) are specifically regulated by MRCK and sensitive to kinase inhibitor chelerynethrine.Multiple diverse functions of MRCK are now known to link to an adaptor protein LRAP35a which appears to have multiple roles in both actomyosin as well as other cytoskeletal regulation.The involvement of cross-talk of MRCK with other signal pathways in cell migration will also be presented.