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Regulation of Rho signaling pathways in interleukin‐2‐stimulated human T‐lymphocytes
Author(s) -
Mzali Rym,
Seguin Laetitia,
Liot Caroline,
Auger Anick,
Pacaud Pierre,
Loirand Gervaise,
Thibault Christelle,
Pierre Josiane,
Bertoglio Jacques
Publication year - 2005
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/fj.05-4030fje
Subject(s) - microbiology and biotechnology , gtpase , signal transduction , biology , cytokinesis , small gtpase , cell cycle , t cell , effector , cell , immune system , immunology , cell division , genetics
Rho GTPases are key regulators of many cellular functions, including cytoskeleton organization which is important for cell morphology and mobility, gene expression, cell cycle progression, and cytokinesis. In addition, it has recently been recognized that Rho GTPase activity is required for development of the immune system, as well as for the specialized functions of the peripheral cells that act in the immune response such as antigen presenting cells and lymphocytes. Stimulation of T lymphocytes with interleukin‐2 (IL‐2) induces clonal expansion of antigen‐specific populations and provides a model to study cell cycle entry and cell cycle progression. We have performed gene expression analysis in a model of human T lymphocytes, which proliferate in response to IL‐2. In addition to changes in genes relevant to cell cycling and to the antiapoptotic effects of IL‐2, we have analyzed expression and variations of more than 300 genes involved in Rho GTPase signaling pathways. We report here that IL‐2 regulates the expression of a number of proteins, which participate in the Rho GTPase pathways, including some of the GTPases themselves, GDP/GTP exchange factors, GTPase activating proteins, as well as GDIs and effectors. Our results suggest that regulation of expression of components of the Rho GTPase pathways may be an important mechanism in assembling specific signal transduction cascades that need to be active at certain times during the cell cycle. Some of our findings may also be relevant to the roles of Rho GTPases in T lymphocyte functions and proliferation.