title: Human substance P receptor undergoes agonist-dependent phosphorylation by G protein-coupled receptor kinase 5 in vitro.
abstract: G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G protein-coupled receptors, leading to receptor desensitization. Seven GRKs, designated GRK1 through 7, have been characterized. GRK5 is negatively regulated by protein kinase C. We investigated whether human substance P receptor (hSPR) is a substrate of GRK5. We report that membrane-bound hSPR is phosphorylated by purified GRK5, and that both the rate and extent of phosphorylation increase dramatically in the presence of substance P. The phosphorylation has a high stoichiometry (20+/-4 mol phosphate/mol hSPR) and a low K(m) (1.7+/-0.1 nM). These data provide the first evidence that hSPR is a substrate of GRK5.
authors.affiliation: Department of Anesthesiology, Juntendo University, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Warabi
authors.forename: Mark D
authors.initials: MD
authors.lastname: Richardson
authors.forename: William T
authors.initials: WT
authors.lastname: Barry
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Eric D
authors.initials: ED
authors.lastname: Roush
authors.forename: Kinya
authors.initials: K
authors.lastname: Nishimura
authors.forename: Madan M
authors.initials: MM
authors.lastname: Kwatra
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D054774:G-Protein-Coupled Receptor Kinase 5; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D018411:Spodoptera; D013373:Substance P / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D018040:Receptors, Neurokinin-1; D013373:Substance P; D017346:Protein Serine-Threonine Kinases; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human; D019204:GTP-Binding Proteins