Interleukin-2 receptor regulates activation of phosphatidylinositol 3-kinase.
Interleukin-2 (IL-2) stimulates proliferation of T lymphocytes and is involved in the activation of both natural killer and lymphokine-activated killer precursor cells. The intracellular messengers which mediate IL-2-dependent events have not yet been identified. IL-2 receptor is not a protein-tyrosine kinase. Activation of a cellular protein-tyrosine kinase and direct association of a protein-tyrosine kinase activity with the IL-2 receptor occurs within minutes of IL-2 stimulation. We investigated the activation of phosphatidylinositol 3-kinase (PI 3-kinase) in IL-2-mediated signal transduction using the IL-2-dependent murine T-cell line, CTLL-2, and human phytohemagglutinin-stimulated peripheral blood lymphocytes (phytohemagglutinin blasts). Within a minute following stimulation of these cells with IL-2, PI 3-kinase activity could be detected in antiphosphotyrosine (anti-P-Tyr) antibody immunoprecipitates. IL-2 triggered a direct association of PI 3-kinase with the IL-2 receptor as detected in immunoprecipitates using anti-IL-2 receptor beta chain antibody. In vivo labeled CTLL-2 cells have a time-dependent increase in D-3-phosphorylated polyphosphoinositides following stimulation with IL-2. This is the first group of second messengers identified in IL-2-mediated signal transduction.
Remillard
B
B
Deaconess/Joslin Division of Nephrology, New England Deaconess Hospital, Boston, Massachusetts 02215.
Petrillo
R
R
Maslinski
W
W
Tsudo
M
M
Strom
T B
TB
Cantley
L
L
Varticovski
L
L
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010770:Phosphotransferases / Q000378:metabolism*; D019000:Phosphotyrosine; D010835:Phytohemagglutinins / Q000494:pharmacology; D011233:Precipitin Tests; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D015290:Second Messenger Systems; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D019000:Phosphotyrosine; D014443:Tyrosine; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase