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Interaction of angio-associated migratory cell protein with the TPα and TPβ isoforms of the human thromboxane A2 receptor
Date Issued
2011-04
Date Available
2011-09-21T14:27:50Z
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.
Sponsorship
Science Foundation Ireland
Health Research Board
Type of Material
Journal Article
Publisher
Elsevier
Journal
Cell Signalling
Volume
23
Issue
4
Start Page
700
End Page
717
Copyright (Published Version)
2011 Elsevier Inc.
Subject – LCSH
Thromboxanes
Cell receptors
Cell migration
G proteins
Web versions
Language
English
Status of Item
Peer reviewed
ISSN
0898-6568
This item is made available under a Creative Commons License
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Name
Reid et al AAMP MS Cell Signal Rev1 8thDec10ProofedAccepted.pdf
Size
7.77 MB
Format
Owning collection
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