Regulation of myosin phosphatase by a specific interaction with cGMP-dependent protein kinase I alpha

Contraction and relaxation of smooth muscle are regulated by myosin light-c hain kinase and myosin phosphatase through phosphorylation and dephosphoryl ation of myosin light chains. Cyclic guanosine monophosphate (cGMP)-depende nt protein kinase I alpha (cGKI alpha) mediates physiologic relaxation of v ascular smooth muscle in response to nitric oxide and cGMP. It is shown her e that cGKI alpha is targeted to the smooth muscle cell contractile apparat us py a Leucine zipper interaction with the myosin-binding subunit (MBS) of myosin phosphatase. Uncoupling of the cGKI alpha-MBS interaction prevents cGMP-dependent dephosphorylation of myosin light chain, demonstrating that this interaction is essential to the regulation of vascular smooth muscle c ell tone.