Activated PLC-?1 is catalytically induced at LAT but activated PLC-?1 is localized at both LAT- and TCR-containing complexes.

ABSTRACT: Phospholipase C-?1 (PLC-?1) is a key regulator of T cell receptor (TCR)-induced signaling. Activation of the TCR enhances PLC-?1 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-?1, leading to its activation and function at the LAT complex. In this study, we examined the phosphorylation kinetics of LAT and PLC-?1 and the cellular localization of activated PLC-?1. We observed that commencement of the phosphorylation of LAT tyrosine 132 and PLC-?1 tyrosine 783 occurred simultaneously, supporting the current model. However, once begun, PLC-?1 activation occurred more rapidly than LAT tyrosine 132. The association of LAT and PLC-?1 was more transient than the interaction of LAT and Grb2 and a pool of activated PLC-?1 translocated away from LAT to cellular structures containing the TCR. These studies demonstrate that LAT and PLC-?1 form transient interactions that catalyze the activation of PLC-?1, but that activated PLC-?1 resides in both LAT and TCR clusters. Together, this work highlights that our current model is incomplete and the activation and function of PLC-?1 in T cells is highly complex.

SUBMITTER: Cruz-Orcutt N 

PROVIDER: S-EPMC3935424 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature