JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.
Interleukin (IL)-4 and IL-9 regulate the proliferation of T lymphocytes through interactions with their receptors. Previous studies have shown that unknown tyrosine kinases are involved in the proliferative signaling triggered by IL-4 and IL-9. Here we show that IL-4 and IL-9 induce overlapping (170, 130, and 125 kilodalton (kDa)) and distinct (45 and 88/90 kDa, respectively) protein tyrosine phosphorylation in T lymphocytes. We further identify the 170-kDa tyrosine-phosphorylated protein as 4PS/insulin receptor substrate-1-like (IRS-1L) protein and 130-kDa protein as JAK1 kinase. Furthermore, we demonstrate for the first time that JAK1 forms complexes with the IL-4 receptor and 4PS/IRS-1L protein following ligand-receptor interaction. In addition, we demonstrate that IL-9, but not IL-4, induced tyrosine phosphorylation of Stat 91 transcriptional factor. The overlapping and distinct protein tyrosine phosphorylation and activation of the same JAK1 kinase in T lymphocytes strongly suggests that IL-4 and IL-9 share the common signal transduction pathways and that the specificity for each cytokine could be achieved through the unique tyrosine-phosphorylated proteins triggered by individual cytokines.
Yin
T
T
Walther Oncology Center, Indiana University Medical Center, Indianapolis 46202.
Tsang
M L
ML
Yang
Y C
YC
D000818:Animals; D004789:Enzyme Activation; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000378:metabolism; D016906:Interleukin-9 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D053613:Janus Kinase 1; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D019948:Receptors, Interleukin-4; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D055504:Insulin Receptor Substrate Proteins; D016906:Interleukin-9; D007378:Interleukins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1