Regulation of Rho signaling pathways in interleukin-2-stimulated human T-lymphocytes.
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.
Mzali
Rym
R
Inserm U461, Faculté de Pharmacie Paris-XI, Chatenay-Malabry, France.
Seguin
Laetitia
L
Liot
Caroline
C
Auger
Anick
A
Pacaud
Pierre
P
Loirand
Gervaise
G
Thibault
Christelle
C
Pierre
Josiane
J
Bertoglio
Jacques
J
D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D003513:Cycloheximide / Q000494:pharmacology; D018450:Disease Progression; D005434:Flow Cytometry; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007376:Interleukin-2 / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D007376:Interleukin-2; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D064067:Rho Guanine Nucleotide Exchange Factors; D003513:Cycloheximide; D020741:rho GTP-Binding Proteins