ArticleOncogene2001
Caspase-dependent cleavage of the hematopoietic specific adaptor protein Gads alters signalling from the T cell receptor.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Survival and Developmental Progression of Unselected Thymocytes in the Absence of the T-Cell Adaptor Gads.European journal of immunology · 2025Article
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- Bridging the Gap: Modulatory Roles of the Grb2-Family Adaptor, Gads, in Cellular and Allergic Immune Responses.Frontiers in immunology · 2019Review
- A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling.Frontiers in immunology · 2018Article
- Anti-apoptotic role of caspase-cleaved GAB1 adaptor protein in hepatocyte growth factor/scatter factor-MET receptor protein signaling.The Journal of biological chemistry · 2012Article
- Targeted cleavage of signaling proteins by caspase 3 inhibits T cell receptor signaling in anergic T cells.Immunity · 2008Article
- Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells.Molecular and cellular biology · 2003Article
- Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity.Genes & development · 2003Article
- Cloning and characterization of human Src-like adaptor protein 2 and a novel splice isoform, SLAP-2-v.Oncogene · 2003Article
- Many cuts to ruin: a comprehensive update of caspase substrates.Cell death and differentiation · 2003Review
- Functional cooperation between c-Cbl and Src-like adaptor protein 2 in the negative regulation of T-cell receptor signaling.Molecular and cellular biology · 2002Article
- Induced expression and association of the Mona/Gads adapter and Gab3 scaffolding protein during monocyte/macrophage differentiation.Molecular and cellular biology · 2002Article
- The role of Gads in hematopoietic cell signalling.Oncogene · 2001Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gads is a SH2 and SH3 domain-containing, hematopoietic-specific adaptor protein that functions in signalling from the T cell receptor. Gads acts by linking SLP-76, bound by the carboxy-terminal Gads SH3 domain, to tyrosine phosphorylated LAT which contains binding sites for the Gads SH2 domain. Gads is distinguished from Grb2 and the closely related Grap protein by the presence of a 120 amino acid unique region between the SH2 domain and the carboxy terminal SH3 domain. Here we demonstrate that the unique region of Gads contains a capase cleavage site. Induction of apoptosis in lymphocytes results in detectable Gads cleavage by 60 min. Gads cleavage is blocked in vivo by treating cells with a caspase 3 inhibitor. A putative caspase 3 cleavage site was identified within the unique region and mutation of this site prevented Gads cleavage in vitro, and in vivo. The Gads cleavage products retained the predicted binding specificity for SLP-76 and LAT. Expression of the Gads cleavage products in Jurkat T cells inhibited NFAT activation following TCR cross linking. These findings indicate that cleavage of Gads in vivo could function to alter signalling downstream of the T cell receptor by disrupting cross talk between SLP-76 and LAT.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.