Cytoplasm-To-Nucleus Shuttling Of Thyroid Hormone Receptor-β1 (Trβ1) 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-beta1 (TRbeta1, TR) is shown in this report to be regulated by extracellular thyroid hormone at a hormone receptor on cell surface integrin alphav3. 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 (T(4)). RESULTS AND DISCUSSION: TR-GFP translocation in the presence of T(4) requires activation of extracellular-regulated protein kinases 1/2 (ERK1/2). Inhibition of T(4)-binding to alphavbeta3 with anti-alphavbeta3 or Arg-Gly-Asp (RGD) peptide blocks T(4)-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, T(4)-activated ERK1/2 and TR1 move transiently in an immunoprecipitable complex to the nuclei of T(4)-treated cells.