Cytoplasm-To-Nucleus Shuttling Of Thyroid Hormone Receptor-1 (Tr1) Is Directed From A Plasma Membrane Integrin Receptor By Thyroid Hormone

Introduction. In CV-1 cells, shuttling from cytoplasm to nucleus of the nuclear thyroid hormone receptor-1 (TR1, TR) is shown in this report to be regulated by extracellular thyroid hormone at a hormone receptor on cell surface integrin v3. Methods. The receptor was introduced into cells as a GFP-TR1 chimera and intracellular movement of the receptor was monitored by confocal microscopy of cells treated with L-thyroxine (T4). Results and Discussion. TR-GFP translocation in the presence of T4 requires activation of extracellular-regulated protein kinases 1/2 (ERK1/2). Inhibition of T4-binding to v3 with anti-v3 or Arg-Gly-Asp (RGD) peptide blocks T4-stimulated GFP-TR nuclear translocation, as do the hormone-binding inhibitor tetraiodothyroacetic acid (tetrac) and the ERK1/2 inhibitor, PD98059. TR1 is an ERK1/2 substrate. Conclusions. Via a nongenomic mechanism initiated at plasma membrane integrin v3, T4-activated ERK1/2 and TR1 move transiently in an immunoprecipitable complex to the nuclei of T4-treated cells.