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Cell Signal. 2014 Apr;26(4):797-805. doi: 10.1016/j.cellsig.2013.12.022. Epub 2014 Jan 8.

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

Author information

1
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
2
Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States.
3
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.
4
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.

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.

KEYWORDS:

Grb2; LAT; PLC-γ1; Phosphorylation kinetics; TCR

PMID:
24412752
PMCID:
PMC3935424
DOI:
10.1016/j.cellsig.2013.12.022
[Indexed for MEDLINE]
Free PMC Article
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