Proposed distinguishing mechanisms of phosphorylation of regulatory light chain (RLC) in tonic and phasic smooth muscle. (A) Myocytes from smooth muscle with tonic patterns of contractile activity (hVM) initiate contractions by simple phosphorylation of RLC at S19. This is predominantly regulated by Ca2+-dependent activation of MLCK. Return to a lower contractile state can be accomplished by increasing activity of MLCP, which is negatively regulated by ROK. (B) For myocytes obtained from smooth muscle with a phasic pattern of contractility (hUM), contraction is also initiated by MLCK-mediated increase in pRLC, but this is augmented by ROK-mediated phosphorylation of pRLC at T18 to form ppRLC, which enhances energy production from myosin ATPase. In addition, increasing ROK activity strongly inhibits the phosphatase activity of MLCP that is predominantly directed towards ppRLC.