title: Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis.
abstract: The primary structure of the human substance K receptor was established from the sequences of complementary DNA clones isolated from a human jejunal complementary DNA library. It consists of 398 amino acids, including seven putative transmembrane regions. The gene for the human substance K receptor was localized to chromosome region 10p13-10q23, a region with frequent chromosomal abnormalities. The human substance K receptor was expressed in transfected NIH-3T3 cells lacking endogenous substance K receptors, and Scatchard analysis of 125I-labeled substance K binding indicates approximately 100,000 receptors/cell with a single dissociation constant of 12 nM. Covalent cross-linking experiments utilizing 125I-substance K and three different chemical cross-linking reagents (disuccinimidyl suberate, disuccinimidyl tartrate, or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl) demonstrate an apparent molecular weight of 45,000, consistent with little or no N-linked glycosylation. The binding of substance K to its receptor on transfected cells led to a rapid increase in the production of total inositol phosphates and the release of Ca2+ from internal stores. Growth of the cells transfected with the human substance K receptor is stimulated by the addition of substance K to the medium to a level similar to 10% serum. Therefore, the human substance K receptor can function as a growth factor receptor when expressed in mouse 3T3 cells.
authors.affiliation: Department of Pharmacology, New York University School of Medicine, New York 10016.
authors.forename: R M
authors.initials: RM
authors.lastname: Kris
authors.forename: V
authors.initials: V
authors.lastname: South
authors.forename: A
authors.initials: A
authors.lastname: Saltzman
authors.forename: S
authors.initials: S
authors.lastname: Felder
authors.forename: G A
authors.initials: GA
authors.lastname: Ricca
authors.forename: M
authors.initials: M
authors.lastname: Jaye
authors.forename: K
authors.initials: K
authors.lastname: Huebner
authors.forename: J
authors.initials: J
authors.lastname: Kagan
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000502:physiology*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology
chemical_list: D006133:Growth Substances; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015288:Neurokinin A