The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions

Mikaela M Tremblay; Tomye Ollinger; Jon C D Houtman

doi:10.1016/j.cellsig.2020.109790

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The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions

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The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions

Mikaela M Tremblay, Tomye Ollinger and Jon C D Houtman

Cellular signalling, Vol.76, pp.109790-109790

12/2020

DOI: 10.1016/j.cellsig.2020.109790

PMCID: PMC7669716

PMID: 32979494

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https://www.ncbi.nlm.nih.gov/pmc/articles/7669716View

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Abstract

The primary activating receptor for T cells is the T cell receptor (TCR), which is stimulated upon binding to an antigen/MHC complex. TCR activation results in the induction of regulated signaling pathways vital for T cell differentiation, cellular adhesion and cytokine release. A critical TCR-induced signaling protein is the adaptor protein LAT. Upon TCR stimulation, LAT is phosphorylated on conserved tyrosines, which facilitates the formation of multiprotein complexes needed for propagation of signaling pathways. Although the role of the conserved tyrosines in LAT-mediated signaling has been investigated, few studies have examined the role of larger regions of LAT in TCR-induced pathways. In this study, a sequence alignment of 97 mammalian LAT proteins was used to identify several "functional" domains on LAT. Using LAT mutants expressed in Jurkat E6.1 cells, we observed that the membrane proximal, proline-rich region of LAT and the correct order of domains containing conserved tyrosines are necessary for optimal TCR-mediated early signaling, cytokine production, and cellular adhesion. Together, these data show that LAT contains distinct regions whose presence and correct order are required for the propagation of TCR-mediated signaling pathways.

Domain order

Structure/function study

Signal transduction

TCR

T cells

LAT

Details

Title: Subtitle: The membrane proximal proline-rich region and correct order of C-terminal tyrosines on the adaptor protein LAT are required for TCR-mediated signaling and downstream functions
Creators: Mikaela M Tremblay - University of Iowa
Tomye Ollinger - University of Iowa
Jon C D Houtman - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: Cellular signalling, Vol.76, pp.109790-109790
DOI: 10.1016/j.cellsig.2020.109790
PMID: 32979494
PMCID: PMC7669716
NLM abbreviation: Cell Signal
ISSN: 0898-6568
eISSN: 1873-3913
Grant note: R56 AI126493 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 12/2020
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics); Internal Medicine
Record Identifier: 9984297430902771

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