Reconstitution of regulated phosphorylation of FcεRI by a lipid raft-excluded protein-tyrosine phosphatase
Reconstitution of regulated phosphorylation of FcεRI by a lipid raft-excluded protein-tyrosine phosphatase
复制标题
DOI：
10.1074/jbc.m408339200
复制
发表时间：
2005-01-14
影响因子：
4.8
通讯作者：
Baird, B
中科院分区：
文献类型：
--
作者：
Young, RM;Zheng, XM;Baird, B
为了研究抗原介导的交联剂诱导的LYN激酶对IgE-FcepsilonRI酪氨酸磷酸化的精细调控，我们利用FcepsilonRI和LYN在中国仓鼠卵巢细胞中的共表达，导致LYN激酶活性和自发磷酸化水平的升高。我们发现，脂筏排除的跨膜酪氨酸磷酸酶PTPalpha的共表达抑制了Lyn激酶的活性，显著降低了FcepsilonRI的自发磷酸化水平，同时促进了其抗原刺激的磷酸化。其他酪氨酸磷酸酶，包括SHP-1，CD45，和脂筏偏好的PTPalpha嵌合版本，不能重建抗原依赖的FcepsilonRI磷酸化。我们得出结论，底物特异性和膜下位置对于磷酸酶介导的Lyn激酶活性的调节至关重要，该调节支持FcepsilonRI的激活。
To examine the exquisite regulation of IgE-FcepsilonRI tyrosine phosphorylation by Lyn kinase that is stimulated by antigen-mediated cross-linking, we utilized co-expression of FcepsilonRI and Lyn in Chinese hamster ovary cells, which results in high basal levels of Lyn kinase activity and spontaneous phosphorylation of FcepsilonRI. We found that co-expression of a lipid raft-excluded transmembrane tyrosine phosphatase, PTPalpha, suppresses Lyn kinase activity and markedly reduces the level of spontaneous phosphorylation of FcepsilonRI, while facilitating its antigen-stimulated phosphorylation. Other tyrosine phosphatases, including SHP-1, CD45, and a lipid raft-preferring chimeric version of PTPalpha fail to reconstitute antigen-dependent FcepsilonRI phosphorylation. We concluded that both substrate specificity and submembrane location are critical to phosphatase-mediated regulation of Lyn kinase activity that supports activation of FcepsilonRI.