Involvement of SHP-2 in multiple aspects of IL-2 signaling: evidence for a positive regulatory role.

Involvement of SHP-2 in multiple aspects of IL-2 signaling: evidence for a positive regulatory role.
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SHP-2 参与 IL-2 信号传导的多个方面:积极调节作用的证据。

DOI:
10.4049/jimmunol.160.10.4657
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发表时间:
1998
影响因子:
4.4
通讯作者:
J. O'Shea
J. O'Shea
中科院分区:
医学2区
文献类型:
--
作者:
M. Gadina;L. Stancato;C. Bacon;A. Larner;J. O'Shea

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IL-2与其受体的结合激活了几个生化途径,但这些途径是如何联系在一起的还不完全清楚。在这里,我们报告了SHP-2,一个含有酪氨酸磷酸酶的SH2结构域,与IL-2信号级联的不同分子有关。在IL-2刺激下,SHP-2与Grb2和磷脂酰肌醇3-激酶的P85亚单位共沉淀。相反,SHP-2与JAK1和JAK3存在结构性关联。最后,SHP-2的表达增强了STAT依赖的转录激活,而显性负等位基因则抑制了反式激活和IL-2诱导的MAPK(丝裂原活化蛋白激酶)的激活。这些结果表明SHP-2参与了IL-2信号级联的多个途径,并为其正向调节作用提供了证据。
Binding of IL-2 to its receptor activates several biochemical pathways, but precisely how these pathways are linked is incompletely understood. Here, we report that SHP-2, an SH2-domain containing tyrosine phosphatase, associates with different molecules of the IL-2 signaling cascade. Upon IL-2 stimulation, SHP-2 was coimmunoprecipitated with Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. In contrast, SHP-2 was constitutively associated with JAK1 and JAK3. Finally, SHP-2 expression amplified STAT-dependent transcriptional activation whereas a dominant negative allele inhibited transactivation and the IL-2-induced activation of MAPK (mitogen-activated protein kinase). These results demonstrate the involvement of SHP-2 in multiple pathways of the IL-2 signaling cascade and provide evidence for its positive regulatory role.
需要来自白细胞介素 2 受体 γ(c) 链近膜区域的初始信号,激活 Janus 激酶,从而导致 T 细胞增殖。
DOI: 10.1073/pnas.94.5.1878
发表时间: 1997
影响因子: 11.1
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DOI: --
发表时间: 1993
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