SH2D1B

更新于：2025-05-07

基本信息

别名

EAT-2、EAT2、EWS/FLI1-activated transcript 2

+ [3]

简介

Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity).

关联

100 项与 SH2D1B 相关的临床结果

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100 项与 SH2D1B 相关的转化医学

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0 项与 SH2D1B 相关的专利（医药）

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166

项与 SH2D1B 相关的文献（医药）

2025-04-17·GENETICS

Activated SKN-1 alters the aging trajectories of long-lived Caenorhabditis elegans mutants

Article

作者: Curran, Sean P ; Turner, Chris D

AbstractIn the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here, we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the eat-2 model of dietary restriction, and glp-1-dependent loss of germ cell proliferation. A hallmark of animals with constitutive SKN-1 activation is the age-dependent loss of somatic lipids, and this phenotype is linked to a general reduction in survival in animals harboring the skn-1gf allele. Surprisingly, daf-2lf; skn-1gf double mutant animals do not redistribute somatic lipids, which suggests the insulin signaling pathway functions downstream of SKN-1 in the maintenance of lipid distribution. As expected, the eat-2lf allele, which independently activates SKN-1, continues to display somatic lipid depletion in older ages with and without the skn-1gf activating mutation. In contrast, the presence of the skn-1gf allele does not lead to somatic lipid redistribution in glp-1lf animals that lack a proliferating germline. Taken together, these studies support a genetic model where SKN-1 activity is an important regulator of lipid mobilization in response to nutrient availability that fuels the developing germline by engaging the daf-2/insulin receptor pathway.

2025-04-01·Experimental Cell Research

The multifaceted role of CS1 (SLAMF7) in immunoregulation: Implications for cancer therapy and autoimmune disorders

Review

作者: Babamuradova, Zarrina ; Singh, Kamred Udham ; Baldaniya, Lalji ; Alam, Rubyat ; Ballal, Suhas ; Sabarivani, A ; Singh, Abhayveer ; Alshahrani, Mohammad Y ; Sead, Fadhil Faez ; Altalbawy, Farag M A

CS1 (SLAMF7), a pivotal immune receptor, plays a dual role in modulating immune responses in autoimmune diseases and cancer. In autoimmunity, aberrant CS1 signaling contributes to the activation of autoreactive lymphocytes, driving pathologies such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Conversely, in oncology, CS1 serves as a promising immunotherapeutic target, exemplified by the efficacy of the monoclonal antibody Elotuzumab in multiple myeloma. CS1 mediates immune cell functions through intricate signaling pathways, including interactions with EAT-2 and SAP adaptors, which influence cytotoxicity, cytokine production, and immune homeostasis. Beyond cancer and autoimmune diseases, soluble and membrane-bound forms of CS1 are emerging as biomarkers and potential therapeutic targets. Despite significant progress, gaps remain in understanding CS1\u2019s mechanisms, variability in expression, and role in other diseases. This study explores the multifaceted functions of CS1, proposing innovative strategies to leverage its therapeutic potential across diverse pathologies.

2024-12-31·Autophagy Reports

A fluorescent reporter for rapid assessment of autophagic flux reveals unique autophagy signatures during C. elegans post-embryonic development and identifies compounds that modulate autophagy

Article

作者: Luke, Cliff J. ; Zhang, Bo ; Hoang, Hieu ; Perlmutter, David H. ; Dawson, Zachary D. ; Zhang, Jessie R. ; Pak, Stephen C. ; Fielder, Sara M. ; Morrison, Stephanie ; Regmi, Suk ; Sundaramoorthi, Hemalatha ; Silverman, Gary A.

Autophagy is important for many physiological processes; and disordered autophagy can contribute to the pathogenesis of a broad range of systemic disorders. C. elegans is a useful model organism for studying the genetics of autophagy, however, current methods for studying autophagy are labor-intensive and not readily amenable to high-throughput procedures. Here we describe a fluorescent reporter, GFP::LGG-1::mKate2, which is useful for monitoring autophagic flux in live animals. In the intestine, the fusion protein is processed by endogenous ATG-4 to generate GFP::LGG-1 and mKate2 proteins. We provide data indicating that the GFP:mKate ratio is a suitable readout for measuring cellular autophagic flux. Using this reporter, we measured autophagic flux in L1 larvae to day 7 adult animals. We show that basal autophagic flux is relatively low during larval development but increases markedly in reproductive adults before decreasing with age. Furthermore, we show that wild-type, eat-2, and daf-2 mutant animals have distinct autophagic flux profiles through post-embryonic development. Finally, we demonstrate the utility of this reporter by performing a high-content small molecule screen to identify compounds that alter autophagic flux in C. elegans.

项与 SH2D1B 相关的新闻（医药）

2023-02-28

·生物谷

Cell子刊：这个负责酒精代谢的基因，有助于延长寿命

这项研究发现，与酒量相关的酒精脱氢酶ADH-1是促进长寿的下游效应物，其激活足以延长从酵母到人类的健康寿命和最终寿命。这提示我们，ADH-1可能是一个十分重要的抗衰老干预靶点众所周知，喝酒有害健康，许多研究表明，酒精（乙醇）是一种致癌物，喝酒与包括癌症在内的一系列伤害和疾病有关。我们在喝酒后，酒精进入体内，首先被肝脏中的乙醇脱氢酶（ADH）转化为乙醛，乙醛被乙醛脱氢酶（ALDH）转化为乙酸，乙酸最终被转化为二氧化碳和水。通常情况下，人们的ADH酶活性相差不大，而ALDH酶活性则差别较大，因此，ALDH活性是酒量主要决定因素。增加ALDH酶活性能够加速酒精代谢的有毒的中间产物乙醛的转化，减少饮酒对身体的伤害。那么，增加ADH酶活性会有什么益处呢？一项最新研究显示，增加乙醇脱氢酶1（ADH-1）活性可延长寿命。近日，美国弗吉尼亚大学的研究人员在 Cell 子刊 Current Biology 上发表题为：Increased alcohol dehydrogenase 1 activity promotes longevity（增加乙醇脱氢酶1活性可延长寿命）的研究论文。该研究发现了由乙醇脱氢酶（ADH）介导的抗衰老反应（简称AMAR），这种酒精代谢相关的酶在多种长寿秀丽隐杆线虫模型中被激活，并且是长寿表型所必须的。不仅如此，ADH-1同源物在禁食小鼠和人类（多项研究表明禁食促进长寿）中同样被诱导，表明ADH-1在广泛的物种中发挥抗衰老效应。这项研究提示我们，ADH-1可能是一个十分重要的抗衰老干预靶点，可以之为核心开发全新的抗衰老疗法。近年来，全球老龄化程度加剧，抗衰老研究成为了世界生命科学领域关注的前沿和热点。在过去的几十年里，科学家们一直在努力破解人类衰老的秘密，与衰老相关的信号分子被相继发现，并以此衍生了多种抗衰老疗法。然而，这些衰老相关因子大多是上游信号枢纽（如mTOR）或中间转录因子（如FOXO/DAF-16），目前尚不清楚是否有下游效应物对长寿是必要且充分的。具有强大抗衰老作用的下游效应物有助于揭示决定衰老速度的基本机制，并且可能是更安全、更有效的抗衰老靶标。发掘这种长寿的下游效应物的一个十分有吸引力的方法是研究在多种促长寿条件下负责激活抗衰老程序的转录因子（TFs），其中一个突出的抗衰老TF是转录因子EB（TFEB）。在研究衰老的模式生物——秀丽隐杆线虫（C. elegans）中，TFEB的同源物为HLH-30。多项研究显示，激活HLH-30可以延长线虫寿命并减少衰老相关的生物标志物。此外，有研究表明，作为自噬和溶酶体生物发生的主要调节因子，HLH-30通过激活自噬来延长健康和寿命，而自噬被认为是生物体长寿所普遍必须的。在这项最新研究中，研究团队在mxl-3突变的长寿线虫模型（以下简称：mxl-3线虫）发现了与上述研究不同的新现象：由mxl-3驱动的长寿需要HLH-30的活性，而HLH-30是自噬的主要调节因子，研究团队首先假设HLH-30通过激活自噬促进了mxl-3线虫的长寿。但与预期相反，研究团队发现自噬在mxl-3线虫中没有被激活。在这些拥有长寿表型的mxl-3线虫中，自噬和溶酶体活性都不是必需的。简而言之，mxl-3线虫的寿命依赖于HLH-30，但不依赖于自噬。 ADH-1对于延长寿命和健康寿命是必要和充分的与此同时，研究团队意外地发现，编码酒精脱氢酶ADH-1的基因在mxl-3线虫和其他依赖于HLH-30的长寿线虫模型中被诱导，包括热量限制（eat-2突变体）、胰岛素信号缺乏（daf-2缺陷）和生长受限（mTOR抑制）。更重要的是，ADH-1基因对于所有这些抗衰老干预的长寿表型都是必要的，并且过表达ADH-1就足以延长秀丽隐杆线虫的寿命。进一步的研究表明，ADH-1通过代谢有毒的甘油来延长寿命，这种有害物质会随着年龄的增长而不断积累。 ADH-1通过阻止促进衰老的代谢物甘油的积累来延长寿命最后，研究团队还提出证据表明，ADH-1的抗衰老能力可能在物种之间是高度保守的，具有从低等生物到高等动物的广泛性。例如，ADH-1过表达也可以延长酵母的寿命，ADH-1直系同源物在热量受限的小鼠和人类中同样被诱导。 ADH-1在热量限制下被诱导激活，并足以延长酵母的寿命总而言之，这项研究发现，与酒量相关的酒精脱氢酶ADH-1是促进长寿的下游效应物，其激活足以延长从酵母到人类的健康寿命和最终寿命。这提示我们，ADH-1可能是一个十分重要的抗衰老干预靶点，可以以之为核心开发全新的抗衰老疗法。

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