title: Protein tyrosine phosphorylation, cellular Ca2+, and Ca2+ sensitivity for contraction of smooth muscle.
abstract: Our studies are guided by the novel hypothesis that protein tyrosine phosphorylation is an important mechanism for regulating contraction of smooth muscle. Several lines of evidence are reviewed which suggest that enhanced tyrosine phosphorylation participates in mechanisms that regulate cytosolic Ca2+ and Ca2+ sensitivity for contraction. First, vanadate-induced contraction of guinea-pig taenia coli is functionally linked to enhanced protein tyrosine phosphorylation of at least three substrates, apparently resulting from vanadate-mediated inhibition of protein tyrosine phosphatase activity. Second, vanadate-induced contraction is dependent on extracellular Ca2+. Third, increases in cytosolic Ca2+ resulting from stimulation of alpha 1-adrenergic receptors in cultured canine vascular smooth muscle cells are associated with enhanced tyrosine phosphorylation and are inhibited by genistein, a potent inhibitor of tyrosine kinase activity. Fourth, genistein markedly and reversibly suppresses Ca2+ sensitivity for contraction in ileal longitudinal smooth muscle permeabilized with staphylococcal alpha-toxin. Moreover, the same or similar substrates (e.g., 42-45, 70, 80-85, 95, 100, 110, 116, and 205 kDa) are tyrosine phosphorylated in response to Ca2+ or stimulation of muscarinic or alpha 1-adrenergic receptors. Collectively, these data strongly suggest that tyrosine phosphorylation is an important mechanism for regulation of smooth muscle contraction.
authors.affiliation: Department of Medical and Molecular Physiology, School of Medicine, University of Minnesota, Duluth 55812, USA.
authors.forename: J
authors.initials: J
authors.lastname: Di Salvo
authors.forename: G
authors.initials: G
authors.lastname: Pfitzer
authors.forename: L A
authors.initials: LA
authors.lastname: Semenchuk
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology*; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D014443:Tyrosine; D002118:Calcium