Interaction of angio-associated migratory cell protein with the TPα and TPβ isoforms of the human thromboxane A2 receptor

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Title: Interaction of angio-associated migratory cell protein with the TPα and TPβ isoforms of the human thromboxane A2 receptor
Authors: Reid, Helen M.
Wikström, Katarina
Kavanagh, David J.
Mulvaney, Eamon P.
Kinsella, B. Therese
Permanent link: http://hdl.handle.net/10197/3161
Date: Apr-2011
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.
Funding Details: Science Foundation Ireland
Health Research Board
Type of material: Journal Article
Publisher: Elsevier
Copyright (published version): 2011 Elsevier Inc.
Keywords: Thromboxane;Receptor;Angio-associated migratory cell protein;Cell migration;Interactant;Yeast two hybrid;RhoA
Subject LCSH: Thromboxanes
Cell receptors
Cell migration
G proteins
DOI: 10.1016/j.cellsig.2010.12.003
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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