Izuhara K, Harada N
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, California 94304-1104, USA.
Biochem Biophys Res Commun. 1996 Dec 13;229(2):624-9. doi: 10.1006/bbrc.1996.1854.
We have recently demonstrated that c-fes protooncogene product (FES), or a FES-related protein, associates with the interleukin-4 receptor alpha chain (IL-4R alpha) and phosphatidylinositol-3 (PI3) kinase in mouse T cell lines; however, others have demonstrated that PI3 kinase associates with IL-4R alpha through tyrosine phosphorylated insulin receptor substrate (IRS)-2 in other cell types. In order to examine whether IL-4 activates these two distinct PI3 kinase pathways in the same cells, we analyzed association of PI3 kinase with IRS-2, and tyrosine phosphorylation of IRS-2, in a mouse pro-B cell line, Ba/F3, and a mouse mast cell line, MC9. In both cell lines, IL-4 induced tyrosine phosphorylation of IRS-2, association of PI3 kinase with IRS-2, and FES or a FES-related protein. These results indicate that IL-4 activates two distinct PI3 kinase pathways in the same cells. We further identified the critical region in the cytoplasmic domain of IL-4R alpha required for tyrosine phosphorylation of IRS-2.
我们最近证明，在小鼠T细胞系中，原癌基因c-fes的产物（FES）或一种与FES相关的蛋白质与白细胞介素4受体α链（IL-4Rα）和磷脂酰肌醇-3（PI3）激酶相关联；然而，其他人已证明，在其他细胞类型中，PI3激酶通过酪氨酸磷酸化的胰岛素受体底物（IRS）-2与IL-4Rα相关联。为了研究IL-4是否在同一细胞中激活这两条不同的PI3激酶途径，我们分析了PI3激酶与IRS-2的关联以及IRS-2的酪氨酸磷酸化情况，所用细胞为小鼠前B细胞系Ba/F3和小鼠肥大细胞系MC9。在这两种细胞系中，IL-4均诱导了IRS-2的酪氨酸磷酸化、PI3激酶与IRS-2的关联以及FES或一种与FES相关的蛋白质的产生。这些结果表明，IL-4在同一细胞中激活了两条不同的PI3激酶途径。我们进一步确定了IL-4Rα胞质结构域中IRS-2酪氨酸磷酸化所需的关键区域。
