Ikizawa K, Yanagihara Y
Clinical Research Center for Allergy, National Sagamihara Hospital, Sagamihara, Kanagawa, 228-8522, Japan.
Biochem Biophys Res Commun. 2000 Feb 5;268(1):54-9. doi: 10.1006/bbrc.2000.2080.
The IL-4Ralpha contains the I4R motif which binds to the phosphotyrosine binding domain of several adaptor proteins, including IRS-1/2 and Shc. Although the involvement of IRS-1/2 in IL-4-induced PI3-kinase activation is known, there is little information on the role of Shc in IL-4 signaling. In this study, we found the preferential utilization of Shc by the IL-4Ralpha in a human Burkitt's B lymphoma cell line, DND39. IL-4 induced the association of tyrosine-phosphorylated Shc with the IL-4Ralpha, whereas no detectable tyrosine phosphorylation of IRS-1 or IRS-2 was induced. IL-4-induced germline epsilon promoter activation was enhanced by overexpression of Shc and was inhibited by truncated Shc lacking the collagen-homologous domain. We further found the association of Shc with PLCgamma1. Although direct tyrosine phosphorylation of PLCgamma1 was not detectable, the amount of PLCgamma1 coprecipitable with anti-phosphotyrosine was increased after IL-4 stimulation. These results suggest that Shc can function as an adaptor protein of the IL-4Ralpha and mediate the germline epsilon transcription.
白细胞介素-4受体α（IL-4Rα）含有I4R基序，该基序可与包括胰岛素受体底物-1/2（IRS-1/2）和Shc在内的几种衔接蛋白的磷酸酪氨酸结合结构域结合。尽管已知IRS-1/2参与白细胞介素-4诱导的磷脂酰肌醇-3激酶（PI3-激酶）激活，但关于Shc在白细胞介素-4信号传导中的作用却知之甚少。在本研究中，我们发现IL-4Rα在人伯基特B淋巴瘤细胞系DND39中优先利用Shc。白细胞介素-4诱导酪氨酸磷酸化的Shc与IL-4Rα缔合，而未诱导IRS-1或IRS-2的可检测到的酪氨酸磷酸化。Shc的过表达增强了白细胞介素-4诱导的种系ε启动子激活，而缺乏胶原同源结构域的截短型Shc则抑制了这种激活。我们进一步发现Shc与磷脂酶Cγ1（PLCγ1）缔合。尽管未检测到PLCγ1的直接酪氨酸磷酸化，但白细胞介素-4刺激后，与抗磷酸酪氨酸共沉淀的PLCγ1量增加。这些结果表明，Shc可作为IL-4Rα的衔接蛋白发挥作用，并介导种系ε转录。
