相关实验视频

Updated: Jun 2, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

在淋巴细胞细胞系中用于BTK信号的膜结合模块的二元化条件要求

Timothy J Eisen^1,2,3, Sam Ghaffari-Kashani^1,2, Chien-Lun Hung^3,4

¹Department of Chemistry, University of California, Berkeley, CA, USA.

Science signaling

|January 14, 2025

概括

布鲁顿的氨酸激酶 (BTK) 信号在细胞类型之间有所不同. 在B细胞中,增加的膜结合,而不是PH-TH二分化,驱动BTK功能,而T细胞需要二分化和激酶活动.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
生物化学生物化学

背景情况:

布鲁顿的氨酸激酶 (BTK) 对于免疫细胞信号传递至关重要,也是重要的药物标.
在BTK介导膜结合的pleckstrin同质和tec同质 (PH-TH) 领域,并涉及到酶活性调节.
已知BTK PH-TH 域二元化可在体外增强激酶活性.

研究的目的:

通过其PH-TH模块在细胞环境 (拉莫斯B细胞和Jurkat T细胞) 中研究BTK二元化.
确定BTK PH-TH 分解和激酶活性是否对于这些细胞类型的BTK信号传递至关重要.
探索BTK PH-TH 分解的进化起源和调节作用.

主要方法:

开发高通量突变发生试验,以评估BTK功能.
在BTK的PH-TH模块和激酶域中测量数千个点突变的适应性成本.
在拉莫斯B细胞和Jurkat T细胞中对BTK功能进行比较分析,并进行进化分析.

主要成果:

在拉莫斯B细胞中,BTK信号传递独立于PH-TH二分化和激酶活性;突变增加了膜吸附增强了信号传递.
在Jurkat T细胞中,BTK信号传递依赖于PH-TH二元化和激酶活性.
进化分析显示,PH-TH二分化是BTK的后期适应,在早期的脊椎动物中不存在.

结论:

BTK信号调节是特定于细胞类型的,在B细胞和T细胞中有不同的机制.
PH-TH二元化代表了在复杂的适应性免疫系统中加强对BTK活动的调节控制的进化发展.
了解这些差异对于有针对性的BTK抑制疗法至关重要.

更多相关视频

Real-time Live Imaging of T-cell Signaling Complex Formation

Real-time Live Imaging of T-cell Signaling Complex Formation

Published on: June 23, 2013

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

Published on: June 13, 2014

相关概念视频

The JAK-STAT Signaling Pathway

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...

Receptor Tyrosine Kinases

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...

Assembly of Signaling Complexes

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...

TGF - β Signaling Pathway

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...

Receptor Downregulation in MVBs

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...