Interleukin‐4‐specific signal transduction events are driven by homotypic interactions of the interleukin‐4 receptor alpha subunit.
Interleukin‐4‐specific signal transduction events are driven by homotypic interactions of the interleukin‐4 receptor alpha subunit.
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IL-4 特异性信号转导事件是由 IL-4 受体 α 亚基的同型相互作用驱动的。
作者：
S. Y. Lai;J. Molden;Kathleen D. Liu;Jennifer M. Puck;Morris D. White;Mark A. Goldsmith
白介素4(IL-4)通过异二聚体受体复合体(IL-4R)发挥作用，该复合体包含IL-4R(α)和γ(C)亚单位。IL-4R(α)也在几种受体类型中与其他伙伴亚单位一起发挥作用，包括IL-13受体。为了研究IL-4R复合体中单个亚基的作用，我们采用了一个嵌合系统，该系统概括了天然IL-4R的功能，通过激活激酶JAK1和JAK3以及诱导STAT-6来验证。当四个细胞质酪氨酸转化为苯丙氨酸的突变的伽马(C)亚单位与IL-4R(α)链的细胞质结构域配对时，JAK-STAT途径的特异性没有改变。在单独表达IL-4R(α)嵌合体的细胞中进一步检测了信号事件，而不表达伽马(C)嵌合体。配体诱导的这些受体的同源二聚激活了IL-4信号程序，包括JAK1和STAT-6的诱导，胰岛素相关底物1的磷酸化和细胞增殖。因此，IL-4R(α)亚基的同型相互作用足以启动和确定IL-4特异的信号事件，并且这种相互作用可能是通过IL-4R复合体进行信号传递所必需的。
Interleukin‐4 (IL‐4) exerts its effects through a heterodimeric receptor complex (IL‐4R), which contains the IL‐4R(alpha) and gamma(c) subunits. IL‐4R(alpha) also functions with other partner subunits in several receptor types, including the IL‐13 receptor. To examine the roles of the individual subunits within IL‐4R complexes, we employed a chimeric system that recapitulates native IL‐4R function as verified by the activation of the kinases, JAK1 and JAK3, and induction of STAT‐6. When a mutant gamma(c) subunit in which the four cytoplasmic tyrosines were converted to phenylalanine was paired with the cytoplasmic domain of the IL‐4R(alpha) chain, specificity within the JAK‐STAT pathway was not altered. Signaling events were examined further in cells expressing the IL‐4R(alpha) chimera alone without the gamma(c) chimera. Ligand‐induced homodimerization of these receptors activated the IL‐4 signaling program despite the absence of gamma(c), including induction of JAK1 and STAT‐6, phosphorylation of the insulin‐related substrate 1 and cellular proliferation. Thus, homotypic interactions of the IL‐4R(alpha) subunit are sufficient for the initiation and determination of IL‐4‐specific signaling events, and such interactions may be integral to signaling through IL‐4R complexes.
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IL-2 信号传导机制：通过单一受体和转导途径介导不同结果。
DOI：
10.1126/science.2492678
发表时间：
1989
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tigges,MA;Casey,LS;Koshland,ME
通讯作者：
Koshland,ME
人白细胞介素 4 受体关键信号传导域的突变分析。
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
生长和基因表达主要由人类 IL-4 受体的不同区域控制。
影响因子：
32.4
作者：
Ryan,JJ;McReynolds,LJ;Keegan,A;Wang,LH;Garfein,E;Rothman,P;Nelms,K;Paul,WE
通讯作者：
Paul,WE
IL-2 受体 γ C 链不作为 IL-4 和 IL-13 受体共享的亚基发挥作用。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
He,YW;Malek,TR
通讯作者：
Malek,TR