PMID- 10567269 OWN - NLM STAT- MEDLINE DCOM- 19991209 LR - 20190619 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 286 IP - 5444 DP - 1999 Nov 19 TI - Regulation of myosin phosphatase by a specific interaction with cGMP- dependent protein kinase Ialpha. PG - 1583-7 AB - Contraction and relaxation of smooth muscle are regulated by myosin light-chain kinase and myosin phosphatase through phosphorylation and dephosphorylation of myosin light chains. Cyclic guanosine monophosphate (cGMP)-dependent protein kinase Ialpha (cGKIalpha) mediates physiologic relaxation of vascular smooth muscle in response to nitric oxide and cGMP. It is shown here that cGKIalpha is targeted to the smooth muscle cell contractile apparatus by a leucine zipper interaction with the myosin-binding subunit (MBS) of myosin phosphatase. Uncoupling of the cGKIalpha-MBS interaction prevents cGMP-dependent dephosphorylation of myosin light chain, demonstrating that this interaction is essential to the regulation of vascular smooth muscle cell tone. FAU - Surks, H K AU - Surks HK AD - Molecular Cardiology Research Institute and Cardiology Division, Department of Medicine, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111, USA. FAU - Mochizuki, N AU - Mochizuki N FAU - Kasai, Y AU - Kasai Y FAU - Georgescu, S P AU - Georgescu SP FAU - Tang, K M AU - Tang KM FAU - Ito, M AU - Ito M FAU - Lincoln, T M AU - Lincoln TM FAU - Mendelsohn, M E AU - Mendelsohn ME LA - eng GR - HL09330/HL/NHLBI NIH HHS/United States GR - HL55309/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Histones) RN - 0 (Isoenzymes) RN - 0 (Myosin Light Chains) RN - 0 (Recombinant Fusion Proteins) RN - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinase Type I) RN - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases) RN - EC 2.7.11.12 (PRKG1 protein, human) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.53 (Myosin-Light-Chain Phosphatase) SB - IM MH - Amino Acid Motifs MH - Amino Acid Substitution MH - Animals MH - Cells, Cultured MH - Cyclic GMP-Dependent Protein Kinase Type I MH - Cyclic GMP-Dependent Protein Kinases/chemistry/genetics/*metabolism MH - Histones/metabolism MH - Humans MH - Isoenzymes/chemistry/metabolism MH - Leucine Zippers MH - Muscle Contraction MH - Muscle Relaxation MH - Muscle, Smooth, Vascular/*enzymology/physiology MH - Mutagenesis, Site-Directed MH - Myosin Light Chains/*metabolism MH - Myosin-Light-Chain Phosphatase MH - Phosphoprotein Phosphatases/chemistry/*metabolism MH - Phosphorylation MH - Precipitin Tests MH - Rats MH - Recombinant Fusion Proteins/metabolism MH - Substrate Specificity MH - Transfection MH - Two-Hybrid System Techniques EDAT- 1999/11/24 00:00 MHDA- 1999/11/24 00:01 CRDT- 1999/11/24 00:00 PHST- 1999/11/24 00:00 [pubmed] PHST- 1999/11/24 00:01 [medline] PHST- 1999/11/24 00:00 [entrez] AID - 8013 [pii] AID - 10.1126/science.286.5444.1583 [doi] PST - ppublish SO - Science. 1999 Nov 19;286(5444):1583-7. doi: 10.1126/science.286.5444.1583.