Interleukin-4 (IL-4) induces protein tyrosine phosphorylation of the IL-4 receptor and association of phosphatidylinositol 3-kinase to the IL-4 receptor in a mouse T cell line, HT2.
To study the signal transduction mechanism of interleukin-4 (IL-4), we have examined the effects of IL-4 on protein tyrosine phosphorylation in a mouse IL-2-dependent T cell line, HT2. Mouse IL-4 induces HT2 proliferation in a dose-dependent manner. Western blotting analyses using anti-phosphotyrosine antibody showed that IL-4 induces tyrosine phosphorylation of four proteins (140, 110, 100, and 92 kDa) in a dose-dependent manner. Protein tyrosine phosphorylation was detected within 1 min and reached a plateau approximately at 10 min after IL-4 stimulation. Immunoprecipitation using anti-IL-4 receptor antibody revealed that the 140-kDa tyrosine-phosphorylated protein is the IL-4 receptor (IL-4R) itself. Furthermore, we demonstrate that phosphatidylinositol 3-kinase (PI 3-kinase) activity in immunoprecipitates with anti-IL-4R antibody increases after IL-4 stimulation. These data indicate that IL-4 induces activation of tyrosine kinase and also induces association between IL-4R and PI 3-kinase.
Izuhara
K
K
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304-1104.
Harada
N
N
D000818:Animals; D002460:Cell Line; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D011233:Precipitin Tests; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D007376:Interleukin-2; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D014443:Tyrosine; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases