Recruitment and activation of PLCγ1 in T cells:: a new insight into old domains

Engagement of the T- cell antigen receptor leads to recruitment of phospholipase C gamma 1 ( PLC gamma 1) to the LAT- nucleated signaling complex and to PLC gamma 1 activation in a tyrosine phosphorylation- dependent manner. The mechanism of PLC gamma 1 recruitment and the role of PLC gamma 1 Src homology ( SH) domains in this process remain incompletely understood. Using a combination of biochemical methods and real- time fluorescent imaging, we show here that the N- terminal SH2 domain of PLC gamma 1 is necessary but not sufficient for its recruitment. Either the SH3 or C- terminal SH2 domain of PLC gamma 1, with the participation of Vav1, c- Cbl and Slp76, are required to stabilize PLC gamma 1 recruitment. All three PLC gamma 1 SH domains are required for phosphorylation of PLC gamma 1 Y783, which is critical for enzyme activation. These novel findings entailed revision of the currently accepted model of PLC gamma 1 recruitment and activation in T lymphocytes.