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The sphingosine 1‐phosphate receptor S1P 4 regulates cell shape and motility via coupling to G i and G 12/13
Author(s) -
Gräler Markus H.,
Grosse Robert,
Kusch Angelika,
Kremmer Elisabeth,
Gudermann Thomas,
Lipp Martin
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10537
Subject(s) - microbiology and biotechnology , sphingosine 1 phosphate , sphingosine , pertussis toxin , sphingosine 1 phosphate receptor , g protein , receptor , biology , g protein coupled receptor , heterotrimeric g protein , motility , signal transduction , biochemistry
Abstract Sphingosine 1‐phosphate (S1P) receptors represent a novel subfamily of G‐protein‐coupled receptors binding S1P specifically and with high affinity. Although their in vivo functions remain largely unknown, in vitro extracellular application of S1P induces distinct S1P receptor‐dependent cellular responses including proliferation, differentiation, and migration. We have analyzed signaling pathways engaged by S1P 4 , which is highly expressed in the lymphoid system. Here we show that S1P 4 couples directly to Gα i and even more effectively to Gα 12/13 ‐subunits of trimeric G‐proteins, but not to Gα q unlike other S1P receptors. Consequently, CHO‐K1 cells ectopically expressing S1P 4 potently activate the small GTPase Rho and undergo cytoskeletal rearrangements, inducing peripheral stress fiber formation and cell rounding, upon S1P stimulation. Overexpression of S1P 4 in Jurkat T cells induces pertussis toxin‐sensitive cell motility even in the absence of exogenously added S1P. In addition, S1P 4 is internalized upon binding of S1P. The capacity of S1P 4 to mediate cellular responses, such as motility and shape change through Gα i ‐ and Gα 12/13 ‐coupled signaling pathways may be important for its in vivo function which is currently under investigation. © 2003 Wiley‐Liss, Inc.