IG-ALPHA AND IG-BETA ARE FUNCTIONALLY HOMOLOGOUS TO THE SIGNALING PROTEINS OF THE T-CELL RECEPTOR
IG-ALPHA AND IG-BETA ARE FUNCTIONALLY HOMOLOGOUS TO THE SIGNALING PROTEINS OF THE T-CELL RECEPTOR
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DOI：
10.1128/mcb.14.2.1095
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发表时间：
1994-02-01
影响因子：
5.3
通讯作者：
NUSSENZWEIG, MC
中科院分区：
文献类型：
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作者：
BURKHARDT, AL;COSTA, T;NUSSENZWEIG, MC
抗原受体和某些Pc受体的信号转导需要受体相关跨膜辅助蛋白家族的激活。这些辅助分子的胞质结构域的一个共同特征是存在至少两个YXXA重复，其是与含Src同源2结构域的蛋白相互作用的潜在位点。然而，不同受体相关蛋白之间的相似程度从同源的T细胞受体（TCR）ζ和Pc受体RIIIA γ链到B细胞抗原受体的远亲IG α和IG β蛋白的相似程度不同。为了确定T细胞和B细胞抗原受体是否在功能上同源，我们研究了带有IG α或IG β胞质结构域的嵌合免疫球蛋白的信号转导。我们发现，伊加和IG β胞质结构域能够激活Ca 2+流动、白细胞介素1分泌和与转染的T细胞中的TCR相同的细胞底物组的磷酸化。然后使用嵌合蛋白来检查T细胞中Fyn、Lck和ZAP激酶活化的最低要求。IG α和IG β都能够直接触发Fyn、Lck和ZAP，而不涉及TCR组分。IG β中的胞质酪氨酸残基是募集和激活ZAP-70所必需的，但这些氨基酸对于Fyn和Lck的激活不是必需的。我们的结论是，Fyn和Lck能够识别成簇的非磷酸化免疫识别受体，但这些激酶的激活是不足以诱导细胞反应，如Ca2+流量和白细胞介素-2分泌。此外，参与抗原受体信号传导途径的分子结构在T和B细胞之间是保守的。
Signal transduction by antigen receptors and some Pc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction with Src homology 2 domain-containing proteins. However, the degree of similarity between the different receptor-associated proteins varies from that of T cell receptor (TCR) zeta and Pc receptor RIIIA gamma chains, which are homologous, to the distantly related Ig alpha and Ig beta proteins of the B-cell antigen receptor. To determine whether T- and B-cell antigen receptors are in fact functionally homologous, we have e studied signal transduction by chimeric immunoblogulins bearing the Ig alpha or Ig beta cytoplasmic domain. We found that Iga and Ig beta cytoplasmic domains were able to activate Ca2+ flux, interleukin l secretion, and phosphorylation of the same group of cellular substrates as the TCR in transfected T cells. Chimeric proteins were then used to examine the minimal requirements for activation of the Fyn, Lck, and ZAP kinases in T cells. Both Ig alpha and Ig beta were able to trigger Fyn, Lck, and ZAP directly without involvement of TCR components. Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP-70, but these amino acids were not essential for the activation of Fyn and Lck. We conclude that Fyn and Lck are able to recognize a clustered nonphosphorylated immune recognition receptor, but activation of these kinases is not sufficient to induce cellular responses such as Ca2+ flux and interleukin-2 secretion. In addition, the molecular structures involved in antigen receptor signaling pathways are conserved between T and B cells.