A novel Zap70 mutation with reduced protein stability demonstrates the rate-limiting threshold for Zap70 in T-cell receptor signalling
نویسندگان
چکیده
منابع مشابه
CBAP Functions as a Novel Component in Chemokine-Induced ZAP70-Mediated T-Cell Adhesion and Migration
Activated chemokine receptor initiates inside-out signaling to transiently trigger activation of integrins, a process involving multiple components that have not been fully characterized. Here we report that GM-CSF/IL-3/IL-5 receptor common beta-chain-associated protein (CBAP) is required to optimize this inside-out signaling and activation of integrins. First, knockdown of CBAP expression in h...
متن کاملRegulatory T cells Suppress Zap70 Phosphorylation in Responding T cells
Objective: Regulatory T cells (Treg) have a critical role in controlling responding T cells (Tresp), thereby preventing autoimmune manifestations including those observed in adenosine deaminase (ADA) enzyme-deficient patients and mice (ADA-KO). Treg suppress various functions of Tresp such as proliferation, cytokine production and expression of activation markers, yet it is not known if Treg su...
متن کاملT cell activation-induced CrkII binding to the Zap70 protein tyrosine kinase is mediated by Lck-dependent phosphorylation of Zap70 tyrosine 315.
The Zap70 protein tyrosine kinase controls TCR-linked signal transduction pathways and is critical for T cell development and responsiveness. Following engagement of TCR, the Zap70 undergoes phosphorylation on multiple tyrosine residues that are implicated in the regulation of its catalytic activity and interaction with signaling effector molecules downstream of the TCR. We have shown previousl...
متن کاملCross-talk between DNA methylation and active histone modifications regulates aberrant expression of ZAP70 in CLL
Zeta-associated protein of 70 kD (ZAP70) is a recognized adverse prognostic marker in chronic lymphocytic leukaemia (CLL) associated with enhanced B-cell receptor signalling, significantly more aggressive disease course and poor overall survival. Zeta-associated protein of 70 kD is ordinarily expressed in T cells where it has a crucial role in T-cell receptor signalling, whereas its aberrant ex...
متن کاملDestabilizing the autoinhibitory conformation of Zap70 induces up-regulation of inhibitory receptors and T cell unresponsiveness
Zap70 plays a critical role in normal T cell development and T cell function. However, little is known about how perturbation of allosteric autoinhibitory mechanisms in Zap70 impacts T cell biology. Here, we analyze mice with a hypermorphic Zap70 mutation, W131A, which destabilizes the autoinhibitory conformation of Zap70, rendering the kinase in a semiactive state. W131A mutant mice with wild-...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Immunology
سال: 2014
ISSN: 0019-2805
DOI: 10.1111/imm.12199