Protein kinase C: a second E-C coupling pathway in vascular smooth muscle? News Physiol

Smooth muscle excitation-contraction (E-C) coupling cannot be easily explained by myosin phosphorylation-dephosphorylation alone. Protein kinase C (PKC) may function as a second signaling pathway. Experimental tools that modify PKC activity differ markedly in specificity and utility. Spatial distribution and possible physiological substrates of PKC are discussed. Evidence for a second E-C coupling pathway Myosin light chain (MLCJ kinase pathway. There is little doubt that Ca”-dependent MLC phosphoryla-tion represents a major pathway by which vascular tone is regulated. The question is whether this is the only pathway involved. As is shown in Fig. 1, activation of MLC kinase results in phosphorylation of the 20-kDa MLC and stimulation of the ac-tin-activated Mg’+-ATPase of myo-sin that promotes smooth muscle contraction. At low intracellular free Ca2+ concentrations ([Ca2+]i), a Ca’+-independent phosphatase dephos-phorylates the light chains to com-plete the cycle (for review see Ref. 13). The relationship between [Ca2+]i, myosin phosphorylation, and active stress appears to be complex, and many dissociations have been re-ported. It is possible that these ap-parent dissociations are not due to the existence of a “second regulatory pathway ” but rather due either to 1) a change in the Ca2+ sensitivity of MLC kinase/phosphatase or 2) changes in the kinetics of cross-bridge attachment/detachment with MLC phosphorylation. REGULATION OF MLC KINASE/PHOS-PHATASE. It had previously been thought that MLC kinase was regu