Interaction of angio-associated migratory cell protein with the TPα and TPβ isoforms of the human thromboxane A₂ receptor.
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.
Mesh Terms:
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, Actinin, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Base Sequence, Carrier Proteins, Cell Movement, Cells, Cultured, Gene Knockdown Techniques, Humans, Molecular Sequence Data, Myocytes, Smooth Muscle, Protein Binding, Protein Interaction Domains and Motifs, Protein Isoforms, RNA, Small Interfering, Receptors, Antigen, B-Cell, Receptors, Thromboxane A2, Prostaglandin H2, Recombinant Fusion Proteins, Thromboxane A2, rhoA GTP-Binding Protein
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, Actinin, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Base Sequence, Carrier Proteins, Cell Movement, Cells, Cultured, Gene Knockdown Techniques, Humans, Molecular Sequence Data, Myocytes, Smooth Muscle, Protein Binding, Protein Interaction Domains and Motifs, Protein Isoforms, RNA, Small Interfering, Receptors, Antigen, B-Cell, Receptors, Thromboxane A2, Prostaglandin H2, Recombinant Fusion Proteins, Thromboxane A2, rhoA GTP-Binding Protein
Cell. Signal.
Date: Apr. 01, 2011
PubMed ID: 21172430
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