TI - Ca2+ -dependent and Ca2+-independent regulation of smooth muscle contraction . AB - An increase in the cytosolic Ca2+ concentration is a prerequisite in activation of contractile activity of smooth muscle . The shape of the Ca2+-signal is determined by spatial distribution and kinetics of Ca2+ -binding sites in the cell . The increase in cytosolic Ca2+ activates myosin light chain kinase ( MLCK ) which in turn phosphorylates the regulatory light chains of myosin II . This Ca2+ -dependent MLC20 phosphorylation is modulated in a Ca2+-independent manner by inhibiting the constitutive active myosin light chain phosphatase mediated by the monomeric GTPase Rho and the Rho-associated kinase as well as protein kinase C or by increasing its activity through cGMP . Furthermore , the activity of MLCK may be decreased due to phosphorylation by CaM kinase II and perhaps p21 activated protein kinase . Hence , smooth muscle tone appears to be regulated by a network of activating and inactivating intracellular signaling cascades which not only show a temporal but also a spatial activation pattern .