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Distinctive T Cell Suppressive Signals from Nuclearized Type 1 Sphingosine 1‐Phosphate G Protein‐Coupled Receptors
Author(s) -
Liao JiaJun,
Huang MeiChuan,
Goetzl Edward J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a614-b
Subject(s) - microbiology and biotechnology , sphingosine , extracellular , sphingosine 1 phosphate , mapk/erk pathway , intracellular , receptor , sphingosine kinase 1 , biology , signal transduction , chemistry , biochemistry
Sphingosine 1‐phosphate (S1P) from innate immune cells regulates lymphoid organ traffic and tissue migration of T cells through the type 1 S1P G protein‐coupled receptor (S1P 1 ). However, effects of the S1P‐S1P 1 axis on T cell proliferation are highly dependent on the timing of introduction of S1P. We now show that antigen receptor (TCR)‐mediated activation of CD4 T cells translocates plasma membrane (PM) S1P 1 to nuclear membranes along with Gi/o, extracellular signal‐regulated kinase (Erk) ½ and some other signaling proteins. By isolating T cell nuclei with intact membrane envelopes and stimulating them with known intracellular concentrations of S1P, we demonstrated that nuclear S1P 1 and PM S1P 1 transduce opposite effects on T cell signals relevant to proliferation. Nuclear p‐Erk levels are decreased by a mean of 70% when 1μM S1P was added to nuclear S1P 1, but increased 3‐fold by adding 1μM S1P to PM S1P 1 . TCR‐mediated activation of T cells therefore not only eliminates migration responses to S1P by downregulation of PM S1P 1 , but also translocates the S1P‐ S1P 1 axis into the nucleus where S1P may control proliferation, survival and other non‐migration functions. (Grant support from NIH HL‐31809.)