Evidence map›Paper›PMID 25636200›Full record

ArticleCellular signalling2015

GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells.

Mahmood Y Bilal, Elizabeth Y Zhang, Brittney Dinkel, Daimon Hardy, Thomas M Yankee, Jon C D Houtman

Open access · greenAbstract read
In one paragraph

Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. [Latest Findings on the Role of Liquid-Liquid Phase Separation in the Regulation of Immune Cell Activation and Key Signaling].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Mahmood Y BilalInterdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States.
Elizabeth Y ZhangDepartment of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
Brittney DinkelDepartment of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
Daimon HardyDepartment of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
Thomas M YankeeDepartment of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
Jon C D HoutmanInterdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States; Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
University of Iowa · USUniversity of Kansas Medical Center · US

Funding

PREDOCTORAL TRAINING PROGRAM IN IMMUNOLOGYT32AI007485 · NIAID · UNIVERSITY OF IOWA · PI Kevin L Legge · 1995 to 2026
$5.4M
Cooperative SH2 and SH3 domain-mediated interactions at the adaptor protein Grb2R01CA136729 · NCI · UNIVERSITY OF IOWA · PI HOUTMAN, JON C.D. · 2010 to 2014
$1.6M
NCI NIH HHS R01 CA136729NCI NIH HHS R01 CA136729-S1NIAID NIH HHS 5T32 AI007485NIAID NIH HHS T32 AI007485
6 · The paper itself

Abstract

GRB2 related adaptor protein downstream of Shc (GADS) is a member of the GRB2 family of adaptors and is critical for TCR-induced signaling. The current model is that GADS recruits SLP-76 to the LAT complex, which facilitates the phosphorylation of SLP-76, the activation of PLC-γ1, T cell adhesion and cytokine production. However, this model is largely based on studies of disruption of the GADS/SLP-76 interaction and murine T cell differentiation in GADS deficient mice. The role of GADS in mediating TCR-induced signals in human CD4+ T cells has not been thoroughly investigated. In this study, we have suppressed the expression of GADS in human CD4+ HuT78 T cells. GADS deficient HuT78 T cells displayed similar levels of TCR-induced SLP-76 and PLC-γ1 phosphorylation but exhibited substantial decrease in TCR-induced IL-2 and IFN-γ release. The defect in cytokine production occurred because of impaired calcium mobilization due to reduced recruitment of SLP-76 and PLC-γ1 to the LAT complex. Surprisingly, both GADS deficient HuT78 and GADS deficient primary murine CD8+ T cells had similar TCR-induced adhesion when compared to control T cells. Overall, our results show that GADS is required for calcium influx and cytokine production, but not cellular adhesion, in human CD4+ T cells, suggesting that the current model for T cell regulation by GADS is incomplete.

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingAnimalsCalciumCD4-Positive T-LymphocytesCell AdhesionCell LineCells, CulturedCytokinesHumansInterferon-gammaInterleukin-2MicePhospholipase C gammaPhosphoproteinsProtein TransportAdaptor Proteins, Signal TransducingCalciumCytokinesGRAP2 protein, humanInterferon-gammaInterleukin-2Phospholipase C gammaPhosphoproteinsReceptors, Antigen, T-CellSLP-76 signal Transducing adaptor proteinsGRB2 family of adaptorsHuman T cellsPLC-γ1T cell receptor signaling

Identifiers

PMID25636200
PMCPMC4339522
OpenAlexW2023231208

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.