title: Interaction of angio-associated migratory cell protein with the TPα and TPβ isoforms of the human thromboxane A₂ receptor.
abstract: In humans, thromboxane (TX) A₂ signals through the TPα and TPβ isoforms of its G-protein coupled TXA₂ receptor (TP) to mediate a host of (patho)physiologic responses. Herein, angio-associated migratory cell protein (AAMP) was identified as a novel interacting partner of both TPα and TPβ through an interaction dependent on common (residues 312-328) and unique (residues 366-392 of TPβ) sequences within their carboxyl-terminal (C)-tail domains. While the interaction was constitutive in mammalian cells, agonist-stimulation of TPα/TPβ led to a transient dissociation of AAMP from immune complexes which coincided with a transient redistribution of AAMP from its localization in an intracellular fibrous network. Although the GTPase RhoA is a downstream effector of both AAMP and the TPs, AAMP did not influence TP-mediated RhoA or vice versa. Small interfering RNA (siRNA)-mediated disruption of AAMP expression decreased migration of primary human coronary artery smooth muscle cells (1° hCoASMCs). Moreover, siRNA-disruption of AAMP significantly impaired 1° hCoASMC migration in the presence of the TXA₂ mimetic U46619 but did not affect VEGF-mediated cell migration. Given their roles within the vasculature, the identification of a specific interaction between TPα/TPβ and AAMP is likely to have substantial functional implications for vascular pathologies in which they are both implicated.
authors.affiliation: School of Biomolecular and Biomedical Sciences, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Reid
authors.forename: Katarina
authors.initials: K
authors.lastname: Wikström
authors.forename: David J
authors.initials: DJ
authors.lastname: Kavanagh
authors.forename: Eamon P
authors.initials: EP
authors.lastname: Mulvaney
authors.forename: B Therese
authors.initials: BT
authors.lastname: Kinsella
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000185:Actinin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006801:Humans; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000819:agonists / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000378:metabolism; D013928:Thromboxane A2 / Q000819:agonists / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C093492:AAMP protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011947:Receptors, Antigen, B-Cell; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D011993:Recombinant Fusion Proteins; D000185:Actinin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D020742:rhoA GTP-Binding Protein