Mutational analysis of a critical signaling domain of the human interleukin 4 receptor.
Mutational analysis of a critical signaling domain of the human interleukin 4 receptor.
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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
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发表时间：
1994
影响因子：
11.1
通讯作者：
Leder,P
中科院分区：
文献类型：
--
作者：
Seldin,DC;Leder,P
人白细胞介素4受体（hIL-4 R）是细胞因子受体超家族的成员，其由细胞外结构域的保守特征定义。hIL-4 R和该家族其他成员的细胞内结构域缺乏任何可识别的酶基序，尽管已经观察到这些受体的配体依赖性酪氨酸磷酸化。最近的研究表明，细胞因子受体的细胞质部分内富含丝氨酸的酸性结构域可能是信号转导所必需的。使用hIL-4 R的缺失和截短突变体，我们已经探索了一个必需的39个氨基酸的信号传导结构域，该结构域富含酸性氨基酸残基和形成已知丝氨酸/苏氨酸激酶的共识磷酸化位点的丝氨酸残基。为了评估这些基序对信号传导的贡献，我们设计了这些残基的定点突变体。令人惊讶的是，表达缺乏丝氨酸或酸性氨基酸的突变hIL-4 R的细胞保留了表达野生型受体的细胞在hIL-4中增殖的能力。此外，所有六个细胞质酪氨酸都不存在的受体可以发挥作用，这表明受体的酪氨酸磷酸化可能是一种附带现象，而不是信号传导中的必要事件。
The human interleukin 4 receptor (hIL-4R) is a member of a superfamily of cytokine receptors defined by conserved features of their extracellular domains. The intracellular domains of the hIL-4R and of other members of this family lack any recognizable enzymatic motifs, though ligand-dependent tyrosine phosphorylation of these receptors has been observed. Recent studies have suggested that serine-rich and acidic domains within the cytoplasmic portions of cytokine receptors might be required for signal transduction. Using deletion and truncation mutants of the hIL-4R, we have explored an essential 39-amino acid signaling domain that is rich in acidic amino acid residues and in serine residues that form consensus phosphorylation sites for known serine/threonine kinases. To assess the contribution of these motifs to signaling, we engineered site-directed mutants of these residues. Surprisingly, cells expressing mutant hIL-4R lacking either the serine or the acidic amino acids retain the ability of cells expressing the wild-type receptor to proliferate in hIL-4. Furthermore, receptors in which all six cytoplasmic tyrosines are absent can function, suggesting that tyrosine phosphorylation of the receptor may be an epiphenomenon rather than a requisite event in signaling.