Izuhara K, Feldman R A, Greer P, Harada N
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA, USA.
Blood. 1996 Nov 15;88(10):3910-8.
We have previously demonstrated that interleukin-4 (IL-4) induces tyrosine phosphorylation of a protein closely related or identical to the c-fes proto-oncogene product (FES) and association of this protein with the IL-4 receptor alpha chain (IL-4R alpha). IL-4 is known to induce association of phosphatidylinositol-3 (PI3) kinase with the IL-4R alpha. Since FES contains the consensus motifs for PI3 kinase binding, we tested the possibility that FES may associate with PI3 kinase upon IL-4 stimulation. We demonstrate herein that IL-4 stimulation induced rapid association of FES or a related protein with PI3 kinase in mouse T-cell lines. We also show an association of human FES (hFES) with the src homology 2 (SH2) domain of PI3 kinase in a COS7 cell expression system. The in vitro PI3 kinase assay using COS7 cells suggested that hFES partly contributes to the association between the hIL-4R alpha and PI3 kinase. We have further identified the important region in the cytoplasmic domain of the hIL-4R alpha for association of tyrosine-phosphorylated hFES with the hIL-4R alpha and SH2 domain of PI3 kinase using a COS7 cell expression system. These results suggest that FES or a related protein/PI3 kinase pathway may play a role in the pleiotropic effects of IL-4.
我们之前已经证明，白细胞介素-4（IL-4）可诱导一种与c-fes原癌基因产物（FES）密切相关或相同的蛋白质发生酪氨酸磷酸化，并使该蛋白质与IL-4受体α链（IL-4Rα）结合。已知IL-4可诱导磷脂酰肌醇-3（PI3）激酶与IL-4Rα结合。由于FES含有PI3激酶结合的共有基序，我们测试了FES在IL-4刺激下可能与PI3激酶结合的可能性。我们在此证明，IL-4刺激可诱导小鼠T细胞系中FES或相关蛋白质与PI3激酶快速结合。我们还在COS7细胞表达系统中显示了人FES（hFES）与PI3激酶的src同源2（SH2）结构域的结合。使用COS7细胞进行的体外PI3激酶测定表明，hFES部分促成了hIL-4Rα与PI3激酶之间的结合。我们还利用COS7细胞表达系统进一步确定了hIL-4Rα胞质结构域中对于酪氨酸磷酸化的hFES与hIL-4Rα及PI3激酶的SH2结构域结合而言重要的区域。这些结果表明，FES或相关蛋白质/PI3激酶途径可能在IL-4的多效性作用中发挥作用。
