Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase
Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase
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DOI：
10.1182/blood.v88.10.3910.bloodjournal88103910
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发表时间：
1996-11-15
期刊：
影响因子：
20.3
通讯作者：
Harada, N
中科院分区：
文献类型：
--
作者：
Izuhara, K;Feldman, RA;Harada, N
我们先前已经证明，白介素4(IL-4)诱导与原癌基因产物(FES)密切相关或相同的蛋白的酪氨酸磷酸化，并使该蛋白与IL-4受体α链(IL-4Rα)结合。已知IL-4可诱导磷脂酰肌醇-3(P13)激酶与IL-4Rα结合。由于FES包含与P13激酶结合的共同基序，我们测试了在IL-4刺激下FES可能与P13激酶结合的可能性。在此，我们证明了IL-4刺激在小鼠T细胞系中诱导FES或相关蛋白与P13蛋白的快速结合。我们还在COS7细胞表达系统中显示了人FES(HFES)与P13激酶的Src同源2(SH2)结构域的关联。用COS7细胞进行的P13激酶体外分析表明，HFES部分参与了HLL-4Rα和P13激酶之间的联系。我们利用COS7细胞表达系统进一步确定了HLL-4Rα胞浆区域中酪氨酸磷酸化的HFES与P13激酶的HLL-4Rα和SH2区域之间的联系。这些结果表明，FES或相关的蛋白/P13激酶通路可能在IL-4的多效性作用中发挥作用。(C)1996年由美国血液病学会主办。
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 a chain (IL-4R alpha). IL-4 is known to induce association of phosphatidylinositol-3 (P13) kinase with the IL-4R alpha. Since FES contains the consensus motifs for P13 kinase binding, we tested the possibility that FES may associate with P13 kinase upon IL-4 stimulation. We demonstrate herein that IL-4 stimulation induced rapid association of FES or a related protein with P13 kinase in mouse T-cell lines. We also show an association of human FES (hFES) with the src homology 2 (SH2) domain of P13 kinase in a COS7 cell expression system. The in vitro P13 kinase assay using COS7 cells suggested that hFES partly contributes to the association between the hlL-4R alpha and P13 kinase. We have further identified the important region in the cytoplasmic domain of the hlL-4R alpha for association of tyrosine-phosphorylated hFES with the hlL-4R alpha and SH2 domain of P13 kinase using a COS7 cell expression system. These results suggest that FES or a related protein/P13 kinase pathway may play a role in the pleiotropic effects of IL-4. (C) 1996 by The American Society of Hematology.