Johnston J A, Wang L M, Hanson E P, Sun X J, White M F, Oakes S A, Pierce J H, O'Shea J J
Lymphocyte Cell Biology Section, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1995 Dec 1;270(48):28527-30. doi: 10.1074/jbc.270.48.28527.
The signaling molecules insulin receptor substrate (IRS)-1 and the newly described IRS-2 (4PS) molecule are major insulin and interleukin 4 (IL-4)-dependent phosphoproteins. We report here that IL-2, IL-7, and IL-15, as well as IL-4, rapidly stimulate the tyrosine phosphorylation of IRS-1 and IRS-2 in human peripheral blood T cells, NK cells, and in lymphoid cell lines. In addition, we show that the Janus kinases, JAK1 and JAK3, associate with IRS-1 and IRS-2 in T cells. Coexpression studies demonstrate that these kinases can tyrosine-phosphorylate IRS-2, suggesting a possible mechanism by which cytokine receptors may induce the tyrosine phosphorylation of IRS-1 and IRS-2. We further demonstrate that the p85 subunit of phosphoinositol 3-kinase associates with IRS-1 in response to IL-2 and IL-4 in T cells. Therefore, these data indicate that IRS-1 and IRS-2 may have important roles in T lymphocyte activation not only in response to IL-4, but also in response to IL-2, IL-7, and IL-15.
信号分子胰岛素受体底物（IRS）-1和新描述的IRS-2（4PS）分子是主要的胰岛素和白细胞介素4（IL-4）依赖性磷蛋白。我们在此报告，IL-2、IL-7和IL-15以及IL-4能快速刺激人外周血T细胞、NK细胞和淋巴样细胞系中IRS-1和IRS-2的酪氨酸磷酸化。此外，我们发现Janus激酶JAK1和JAK3在T细胞中与IRS-1和IRS-2相关联。共表达研究表明这些激酶可使IRS-2发生酪氨酸磷酸化，提示细胞因子受体可能诱导IRS-1和IRS-2酪氨酸磷酸化的一种可能机制。我们进一步证明，在T细胞中，磷脂酰肌醇3激酶的p85亚基在IL-2和IL-4作用下与IRS-1相关联。因此，这些数据表明，IRS-1和IRS-2不仅在对IL-4的反应中，而且在对IL-2、IL-7和IL-15的反应中，可能在T淋巴细胞激活中发挥重要作用。
