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

In humans, thromboxane (TX) A(2) signals through the TP alpha and TP beta isoforms of its G-protein coupled TXA(2) 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 TP alpha and TP beta through an interaction dependent on common (residues 312-328) and unique (residues 366-392 of TP beta) sequences within their carboxyl-terminal (C)-tail domains. While the interaction was constitutive in mammalian cells, agonist-stimulation of TP alpha/TP beta 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 degrees hCoASMCs). Moreover, siRNA-disruption of AAMP significantly impaired 1 degrees hCoASMC migration in the presence of the TXA(2) mimetic U46619 but did not affect VEGF-mediated cell migration. Given their roles within the vasculature, the identification of a specific interaction between TP alpha/TP beta and AAMP is likely to have substantial functional implications for vascular pathologies in which they are both implicated. (C) 2011 Elsevier Inc. All rights reserved.