期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 50, 页码 21143-21148出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911309106
关键词
substrate recognition; T cell signaling; Tec kinases
资金
- National Institute of Allergy and Infectious Diseases, National Institutes of Health
Interleukin-2 tyrosine kinase (Itk) is a Tec family tyrosine kinase that mediates signaling processes after T cell receptor engagement. Activation of Itk requires recruitment to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex. After activation, Itk phosphorylates and activates phospholipase C-gamma 1 (PLC-gamma 1), leading to production of two second messengers, DAG and IP3. We have previously shown that phosphorylation of PLC-gamma 1 by Itk requires a direct, phosphotyrosine-independent interaction between the Src homology 2 (SH2) domain of PLC-gamma 1 and the kinase domain of Itk. We now define this docking interface using a combination of mutagenesis and NMRspectroscopy and show that disruption of the Itk/PLC gamma 1 docking interaction attenuates T cell signaling. The binding surface on PLC gamma 1 that mediates recognition by Itk highlights a nonclassical binding activity of the well-studied SH2 domain providing further evidence that SH2 domains participate in important signaling interactions beyond recognition of phosphotyrosine.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据