Interleukin-13 Signal Transduction in Lymphohemopoietic Cells

Interleukin-13 Signal Transduction in Lymphohemopoietic Cells
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淋巴细胞中的 IL-13 信号转导

DOI:
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发表时间:
1995
影响因子:
4.8
通讯作者:
J. Schrader
J. Schrader
中科院分区:
生物学2区
文献类型:
--
作者:
M. Welham;Leslie Learmonth;H. Bone;J. Schrader

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白细胞介素-13(IL-13)和白细胞介素-4(IL-4)在结构和功能上相关,并且被认为共享共同的受体组分。我们已经研究了这两种生长因子以及胰岛素在淋巴造血起源的细胞系和原代细胞中激活的信号转导途径。所有三种因子均诱导170 kDa蛋白(p170)的酪氨酸磷酸化,该蛋白通过p85的SH 2结构域介导的高亲和力相互作用与PI 3 ′-激酶的p85亚基共沉淀。针对整个胰岛素受体底物-1(IRS-1)蛋白的抗体免疫沉淀p170的效率远低于3 T3细胞中的IRS-1。然而,针对IRS-1的保守普列克底物蛋白同源结构域的抗体以相似的效率免疫沉淀p170和IRS-1,表明它们在该区域具有结构相似性。在淋巴造血细胞中,IL-13、IL-4和胰岛素不能诱导Shc酪氨酸磷酸化增加,或其与grb 2、Sos 1修饰或erk-1和erk-2促分裂原活化蛋白激酶的活化相关,表明p170介导的下游途径与IRS-1介导的途径不同。IL-13和IL-4均诱导Tyk-2和Jak-1的低水平酪氨酸磷酸化。IL-4也激活了Jak-3激酶,但是,尽管有其他相似之处,IL-13却没有。胰岛素未能激活Janus激酶家族的任何已知成员。因为据报道Jak-3与IL-2c链缔合,这些数据表明IL-13受体不利用该亚基。然而,IL-13和IL-4均诱导IL-4-140 kDa受体链的酪氨酸磷酸化,表明这是这些细胞中两种受体的组分,并解释了IL-13和IL-4共享的信号传导途径的相似性。
Interleukin-13 (IL-13) and interleukin-4 (IL-4) are related in structure and function and are thought to share a common receptor component. We have investigated the signal transduction pathways activated by these two growth factors, as well as insulin, in cell-lines and primary cells of lymphohemopoietic origin. All three factors induced the tyrosine phosphorylation of a protein of 170 kDa (p170), which coimmunoprecipitated with the p85 subunit of PI3′-kinase, via high affinity interactions mediated by the SH2 domains of p85. Antibodies raised against the entire insulin-receptor substrate-1 (IRS-1) protein immunoprecipitated p170 much less efficiently than they did IRS-1 from 3T3 cells. However, antibodies directed against the conserved pleckstrin homology domain of IRS-1 immunoprecipitated both p170 and IRS-1 with similar efficiency, suggesting they share structural similarities in this region. In lymphohemopoietic cells, IL-13, IL-4, and insulin failed to induce increased tyrosine phosphorylation of Shc, or its association with grb2, modification of Sos1, or activation of erk-1 and erk-2 mitogen-activated protein kinases, suggesting that p170 mediates downstream pathways distinct from those mediated by IRS-1. Both IL-13 and IL-4 induced low levels of tyrosine phosphorylation of Tyk-2 and Jak-1. IL-4 also activated the Jak-3-kinase, but, despite other similarities, IL-13 did not. Insulin failed to activate any of the known members of the Janus family of kinases. In that Jak-3 is reported to associate with the IL-2c chain, these data suggest that the IL-13 receptor does not utilize this subunit. However, both IL-13 and IL-4 induced tyrosine phosphorylation of the IL-4-140 kDa receptor chain, suggesting that this is a component of both receptors in these cells and accounts for the similarities in signaling pathways shared by IL-13 and IL-4.
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发表时间: 1991
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DOI: --
发表时间: 1993
期刊: The Journal of biological chemistry
影响因子: --
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DOI: 10.1073/pnas.91.6.2140
发表时间: 1994
影响因子: 11.1
作者:
Seldin,DC;Leder,P
通讯作者: Leder,P
DOI: 10.1126/science.7694370
发表时间: 1993-11-19
期刊: SCIENCE
影响因子: 56.9
作者:
KOTANIDES, H;REICH, NC
通讯作者: REICH, NC