title: Unfair competition governs the interaction of pCPI-17 with myosin phosphatase (PP1-MYPT1).
abstract: The small phosphoprotein pCPI-17 inhibits myosin light-chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MLCP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interactinhibition by unfair competition:MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP's active site. MLCP dephosphorylates pCPI-17 at a slow rate that is, nonetheless, both sufficient and necessary to explain the speed of pCPI-17 dephosphorylation and the consequent MLCP activation during muscle relaxation.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Filter
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Byron C
authors.initials: BC
authors.lastname: Williams
authors.affiliation: Department of Molecular Physiology and Biophysics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, United States.
authors.forename: Masumi
authors.initials: M
authors.lastname: Eto
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: David
authors.initials: D
authors.lastname: Shalloway
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, United States.
authors.forename: Michael L
authors.identifier: 0000-0003-0200-0277
authors.initials: ML
authors.lastname: Goldberg
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human
keywords: CPI-17; biochemistry; cell biology; human; mouse; myosin phosphatase; smooth muscle contraction/relaxation; unfair competition