Cytoplasm-to-nucleus shuttling of thyroid hormone receptor-beta1 (Trbeta1) is directed from a plasma membrane integrin receptor by thyroid hormone.
BACKGROUND
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)).


CONCLUSIONS
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.
Cao
H James
HJ
Ordway Research Institute, Inc., Albany, New York 12208, USA.
Lin
Hung-Yun
HY
Luidens
Mary K
MK
Davis
Faith B
FB
Davis
Paul J
PJ
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D039302:Integrin alphaVbeta3 / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D013974:Thyroxine / Q000031:analogs & derivatives / Q000494:pharmacology; D014709:Vero Cells
D005419:Flavonoids; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011988:Receptors, Thyroid Hormone; C047981:arginyl-glycyl-aspartic acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C011126:tetraiodothyroacetic acid; D013974:Thyroxine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one