ARAP, a Novel Adaptor Protein, Is Required for TCR Signaling and Integrin-Mediated Adhesion

Jung, Sun Ho; Yoo, Eun Sun; Yu, Meilin; Song, Hyeon Myeong; Kang, Hee Yoon; Cho, Je Yoel; Lee, Jong Ran

doi:10.4049/jimmunol.1501913

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…STK11 gene is a tumor suppressor gene [30]. FYB2 gene, also known as ARAP gene, encodes a T cell adaptor protein mediating cell adhesion [31]. These immunity-related genes were shared between three breeds of cattle.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide SNPs and InDels Characteristics of Three Chinese Cattle Breeds

Zhang

Chen

et al. 2019

Animals

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Simple SummaryWhole-genome resequencing is an important tool to reveal the in-depth genomic characteristics of a genome. Adaptability traits are key to the survival of the south Chinese zebu cattle. However, the potential genetic information behind these remarkable traits still remains uncertain and needs to be addressed. In the current study, we utilized a total of 15 local south Chinese cattle samples (Leiqiong (LQ), Wannan (WN), Wenshan (WS)) from one of our previous studies mapped to the old reference genome (Btau_5.0.1) and remapped them to the latest reference genome (ARS-UCD1.2) to explore potential single nucleotide polymorphisms (SNPs) and insertions-deletions (InDels) responsible for some important immune related traits. The present study emphasizes and illustrates the genetic diversity, extending our previous study. The InDel annotation show that WS cattle had more enriched genes associated with immune functions than the other two breeds. Our findings provide valuable resources for further investigation of the functions of SNP- and InDels-related genes and help to determine the molecular basis of adaptive mutations in Chinese zebu cattle.AbstractWe report genome characterization of three native Chinese cattle breeds discovering ~34.3 M SNPs and ~3.8 M InDels using whole genome resequencing. On average, 10.4 M SNPs were shared amongst the three cattle breeds, whereas, 3.0 M, 4.9 M and 5.8 M were specific to LQ, WN and WS breeds, respectively. Gene ontology (GO)analysis revealed four immune response-related GO terms were over represented in all samples, while two immune signaling pathways were significantly over-represented in WS cattle. Altogether, we found immune related genes (PGLYRP2, ROMO1, FYB2, CD46, TSC1) in the three cattle breeds. Our study provides insights into the genetic basis of Chinese indicine adaptation to the tropic and subtropical environment, and provides a valuable resource for further investigations of genetic characteristics of the three breeds.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide SNPs and InDels Characteristics of Three Chinese Cattle Breeds

Zhang

Chen

et al. 2019

Animals

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“…Once T cells are stimulated, TCR activates the tyrosine kinase ZAP70, and ZAP70 is phosphorylated and activated by LCK. Thereafter, a large number of signal molecules are absorbed, which ultimately leads to the production of lymphokines [ 17 ]. Subsequently, studies have demonstrated that LCK phosphorylation inhibits inflammatory storm via TLR4 signaling pathway [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Screening of key genes related to the prognosis of mouse sepsis

Chen

et al. 2020

Bioscience Reports

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Sepsis is a common clinical disease with high mortality, and patients with sepsis have varied prognoses. Researchers need to explore the underlying mechanisms that determine the prognosis of sepsis. Hence, a mouse model was used to evaluate new potential prognostic markers of sepsis. Mice were randomly divided into low-dose group (n = 3, lipopolysaccharides [LPS], 20mg/kg) and high-dose group (n = 3; LPS, 40mg/kg). Total RNA was extracted from the peripheral blood of mice, and samples were then subjected to RNA sequencing. When complete data were normalized, the high-dose group and low-dose group were screened for differentially expressed genes (DEGs, log2FC ≥ 1 and q value ≤ 0.05). DEGs were analyzed by gene ontology enrichment, and potential core genes were screened using protein–protein interaction network (PPI) and weighted gene co-expression network analysis (WGCNA). Moreover, the survival data in GSE65682 was used to observe the correlation between core genes and prognosis. A total of 967 DEGs were identified in the low-dose group, of which 390 were upregulated and 577 were downregulated. These genes were mainly enriched in white blood cell activation, lymphocyte activation, immune system response, etc. LCK, ZAP70, ITK, CD247, and DOCK2 were found at the core of PPI network, while WGCNA found that IFI35, ITGB3, and MED25 may be potential core genes. It was demonstrated that CD247, DOCK2, IFI35, ITK, and LCK core genes were positively correlated with prognosis based on GSE65682. CD247, DOCK2, IFI35, ITK, LCK, and MED25 might be important targets affecting the prognosis of sepsis.

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“…In 2016, Jung and colleagues identified a novel adapter protein termed ARAP (activation-dependent raft-recruited ADAP-like phosphoprotein) ( 95 ). The ARAP cDNA encodes for a protein of 728 amino acids with a predicted molecular weight of 83 kDa.…”

Section: Adapmentioning

confidence: 99%

“…It was shown, that ARAP is required for TCR/CD3-mediated proximal signaling such as PLCγ1 activation and Ca 2+ release, T-cell adhesion to ICAM-1 but not for TCR/CD3-mediated actin polymerization. In addition, interaction of ARAP with SLP-76, SKAP1, Lck and Fyn was demonstrated ( 95 ). Since confirmatory reports about ARAP are still missing, the biological significance of ARAP in T cells remains elusive.…”

Section: Adapmentioning

confidence: 99%

The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events

et al. 2021

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T cells are the key players of the adaptive immune response. They coordinate the activation of other immune cells and kill malignant and virus-infected cells. For full activation T cells require at least two signals. Signal 1 is induced after recognition of MHC/peptide complexes presented on antigen presenting cells (APCs) by the clonotypic TCR (T-cell receptor)/CD3 complex whereas Signal 2 is mediated via the co-stimulatory receptor CD28, which binds to CD80/CD86 molecules that are present on APCs. These signaling events control the activation, proliferation and differentiation of T cells. In addition, triggering of the TCR/CD3 complex induces the activation of the integrin LFA-1 (leukocyte function associated antigen 1) leading to increased ligand binding (affinity regulation) and LFA-1 clustering (avidity regulation). This process is termed “inside-out signaling”. Subsequently, ligand bound LFA-1 transmits a signal into the T cells (“outside-in signaling”) which enhances T-cell interaction with APCs (adhesion), T-cell activation and T-cell proliferation. After triggering of signal transducing receptors, adapter proteins organize the proper processing of membrane proximal and intracellular signals as well as the activation of downstream effector molecules. Adapter proteins are molecules that lack enzymatic or transcriptional activity and are composed of protein-protein and protein-lipid interacting domains/motifs. They organize and assemble macromolecular complexes (signalosomes) in space and time. Here, we review recent findings regarding three cytosolic adapter proteins, ADAP (Adhesion and Degranulation-promoting Adapter Protein), SKAP1 and SKAP2 (Src Kinase Associated Protein 1 and 2) with respect to their role in TCR/CD3-mediated activation, proliferation and integrin regulation.

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ARAP, a Novel Adaptor Protein, Is Required for TCR Signaling and Integrin-Mediated Adhesion

Cited by 11 publications

References 48 publications

Genome-Wide SNPs and InDels Characteristics of Three Chinese Cattle Breeds

Genome-Wide SNPs and InDels Characteristics of Three Chinese Cattle Breeds

Screening of key genes related to the prognosis of mouse sepsis

The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events

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