Recent advances in the understanding of interleukin-2 signal transduction.
Interleukin-2 is one of the critical cytokines that control the proliferation and differentiation of cells of the immune system. The present article briefly reviews the current and recently established knowledge on the intracellular signaling events that convert the initial interaction of IL-2 with its receptor into pathways leading to the various biological functions. A first step in IL-2 signaling is the activation of several protein tyrosine kinases that phosphorylate a large array of intracellular substrates including the receptor complex. Phosphorylated tyrosine residues within the receptor then serve as docking sites for multimolecular signaling complexes that initiate three major pathways: the Jak-STAT pathway controlling gene transcription, the Ras-MAPK pathway leading to cell proliferation and gene transcription as well, and the PI3-kinase pathway involved in antiapoptotic signaling and organization of the cytoskeleton. Finally, other recently identified and presumably important tyrosine kinase substrates, whose significance is not yet fully understood, are described.
Gesbert
F
F
INSERM Unit 461, Faculté de Pharmacie Paris-XI, Chatenay-Malabry, France.
Delespine-Carmagnat
M
M
Bertoglio
J
J
D048868:Adaptor Proteins, Signal Transducing; D056827:Endosomal Sorting Complexes Required for Transport; D007376:Interleukin-2 / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D056827:Endosomal Sorting Complexes Required for Transport; D007376:Interleukin-2; D010750:Phosphoproteins; D015375:Receptors, Interleukin-2; C109775:STAM protein, human; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases