Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes

Noemi Cruz-Orcutt; Aldo Vacaflores; Sean F Connolly; Stephen C Bunnell; Jon C D Houtman

doi:10.1016/j.cellsig.2013.12.022

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Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes

Journal article

Peer reviewed

Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes

Noemi Cruz-Orcutt, Aldo Vacaflores, Sean F Connolly, Stephen C Bunnell and Jon C D Houtman

Cellular signalling, Vol.26(4), pp.797-805

04/2014

DOI: 10.1016/j.cellsig.2013.12.022

PMCID: PMC3935424

PMID: 24412752

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Abstract

Phospholipase C-γ1 (PLC-γ1) is a key regulator of T cell receptor (TCR)-induced signaling. Activation of the TCR enhances PLC-γ1 enzymatic function, resulting in calcium influx and the activation of PKC family members and RasGRP. The current model is that phosphorylation of LAT tyrosine 132 facilitates the recruitment of PLC-γ1, leading to its activation and function at the LAT complex. In this study, we examined the phosphorylation kinetics of LAT and PLC-γ1 and the cellular localization of activated PLC-γ1. We observed that commencement of the phosphorylation of LAT tyrosine 132 and PLC-γ1 tyrosine 783 occurred simultaneously, supporting the current model. However, once begun, PLC-γ1 activation occurred more rapidly than LAT tyrosine 132. The association of LAT and PLC-γ1 was more transient than the interaction of LAT and Grb2 and a pool of activated PLC-γ1 translocated away from LAT to cellular structures containing the TCR. These studies demonstrate that LAT and PLC-γ1 form transient interactions that catalyze the activation of PLC-γ1, but that activated PLC-γ1 resides in both LAT and TCR clusters. Together, this work highlights that our current model is incomplete and the activation and function of PLC-γ1 in T cells is highly complex.

Phosphorylation

Signal Transduction

Phospholipase C gamma - metabolism

Receptors, Antigen, T-Cell - metabolism

Jurkat Cells

Humans

T-Lymphocytes - metabolism

Protein Binding

T-Lymphocytes - immunology

Membrane Proteins - metabolism

Kinetics

Adaptor Proteins, Signal Transducing - metabolism

GRB2 Adaptor Protein - metabolism

Details

Title: Subtitle: Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes
Creators: Noemi Cruz-Orcutt - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
Aldo Vacaflores - Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
Sean F Connolly - Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States
Stephen C Bunnell - Program in Immunology, Sackler School of Graduate Biomedical Sciences, Boston, MA 02111, United States; Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, United States
Jon C D Houtman - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States; Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States. Electronic address: jon-houtman@uiowa.edu
Resource Type: Journal article
Publication Details: Cellular signalling, Vol.26(4), pp.797-805
DOI: 10.1016/j.cellsig.2013.12.022
PMID: 24412752
PMCID: PMC3935424
ISSN: 0898-6568
eISSN: 1873-3913
Grant note: T32 AI007485 / NIAID NIH HHS R01 CA136729 / NCI NIH HHS
Language: English
Date published: 04/2014
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984094309302771

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