title: The role of alternative splicing and C-terminal amino acids in thromboxane receptor stabilization.
abstract: The thromboxane receptor has two alternatively spliced isoforms, alpha and beta, which differ only in sequences within the cytoplasmic C-terminal domain. Oxidative stress induced by H(2)O(2) in a COS-7 cell model results in stabilization of the thromboxane receptor beta isoform by translocation from the endoplasmic reticulum to the Golgi complex, which in turn results in protection of the receptor from degradation. We now report that both the alpha and beta thromboxane receptor isoforms respond identically to oxidative stress. Further, mutagenesis studies indicate that replacing the normal C-terminus with a nonsense sequence also does not alter stabilization behaviour ruling out a role for the distinct C-termini in this process. Further mutagenesis implicates a cluster of arginine residues within the C-terminal domain as involved in oxidative stress-induced stabilization. These data identify a region of the thromboxane receptor that is responsible for responding to oxidative challenge and open the possibility of identification of the molecular machinery underpinning this response.
authors.affiliation: Division of Cell and Molecular Biology, Biochemistry Building, Imperial College, London SW7 2AZ, UK.
authors.forename: François
authors.initials: F
authors.lastname: Valentin
authors.forename: John R
authors.initials: JR
authors.lastname: Tippins
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D008657:Metabolic Clearance Rate; D016297:Mutagenesis, Site-Directed; D018384:Oxidative Stress / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology*; D017482:Receptors, Thromboxane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D020033:Protein Isoforms; D017482:Receptors, Thromboxane