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Submitted on January 26, 2005
Accepted on March 21, 2005
V
3 Contains a Cell Surface Receptor Site for Thyroid Hormone that is Linked to Activation of MAPK and Induction of Angiogenesis
Ordway Research Institute, 150 New Scotland Avenue, Albany, New York 12208. Stratton Veterans Affairs Medical Center, 113 Holland Avenue, Albany, New York 12208. Albany College of Pharmacy, 106 New Scotland Avenue, Albany, New York 12208. The Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201
* To whom correspondence should be addressed. E-mail: pdavis{at}ordwayresearch.org.
Integrin 
V
3 is a heterodimeric plasma membrane protein whose several extracellular matrix protein ligands contain an RGD recognition sequence. This study identifies integrin V3 as a cell surface receptor for thyroid hormone (L-thyroxine, T4) and as the initiation site for T4-induced activation of intracellular signaling cascades. Integrin V3 dissociably binds radiolabeled T4 with high affinity and this binding is displaced by tetraiodothyroacetic acid (tetrac), V3 antibodies and by an integrin RGD recognition site peptide. CV-1 cells lack nuclear thyroid hormone receptor but express plasma membrane V3; treatment of these cells with physiological concentrations of T4 activates the MAPK pathway, an effect inhibited by tetrac, RGD peptide and V3 antibodies. Inhibitors of T4-binding to the integrin also block the MAPK-mediated pro-angiogenic action of T4. T4-induced phosphorylation of MAPK is inhibited by siRNA knockdown of V and 3. These findings suggest that T4 binds to V3 near the RGD recognition site and show that hormone-binding to V3 has physiologic consequences.
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