Journal article
GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells
Cellular signalling, Vol.27(4), pp.841-850
04/2015
DOI: 10.1016/j.cellsig.2015.01.012
PMCID: PMC4339522
PMID: 25636200
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.
•LAT recruitment but not phosphorylation of SLP-76 and PLC-γ1 requires GADS.•GADS is dispensable for TCR-mediated actin polymerization and cellular adhesion.•GADS is required for TCR-induced calcium influx and cytokine release.•Recruitment and function of PLC-γ1 are impaired in the absence of GADS.
Details
- Title: Subtitle
- GADS is required for TCR-mediated calcium influx and cytokine release, but not cellular adhesion, in human T cells
- Creators
- Mahmood Y Bilal - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United StatesElizabeth Y Zhang - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, United StatesBrittney Dinkel - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesDaimon Hardy - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United StatesThomas M Yankee - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, United StatesJon C.D Houtman - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Cellular signalling, Vol.27(4), pp.841-850
- DOI
- 10.1016/j.cellsig.2015.01.012
- PMID
- 25636200
- PMCID
- PMC4339522
- NLM abbreviation
- Cell Signal
- ISSN
- 0898-6568
- eISSN
- 1873-3913
- Publisher
- Elsevier Inc
- Grant note
- name: National Institutes of Health Predoctoral Training, award: 5T32 AI007485; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 CA136729, RO1 CA136729-S1
- Language
- English
- Date published
- 04/2015
- Academic Unit
- Microbiology and Immunology; Pathology; Internal Medicine
- Record Identifier
- 9984047874702771
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