Recruitment and activation of PLCgamma1 in T cells: a new insight into old domains.
Engagement of the T-cell antigen receptor leads to recruitment of phospholipase Cgamma1 (PLCgamma1) to the LAT-nucleated signaling complex and to PLCgamma1 activation in a tyrosine phosphorylation-dependent manner. The mechanism of PLCgamma1 recruitment and the role of PLCgamma1 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 PLCgamma1 is necessary but not sufficient for its recruitment. Either the SH3 or C-terminal SH2 domain of PLCgamma1, with the participation of Vav1, c-Cbl and Slp76, are required to stabilize PLCgamma1 recruitment. All three PLCgamma1 SH domains are required for phosphorylation of PLCgamma1 Y783, which is critical for enzyme activation. These novel findings entailed revision of the currently accepted model of PLCgamma1 recruitment and activation in T lymphocytes.
Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4254, USA.
Alex
A
Braiman
Mira
M
Barda-Saad
Connie L
CL
Sommers
Lawrence E
LE
Samelson
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D008856:Microscopy, Fluorescence; D051966:Phospholipase C gamma / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000276:immunology; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology; D051567:Proto-Oncogene Proteins c-vav / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D018909:src Homology Domains / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D051567:Proto-Oncogene Proteins c-vav; D011948:Receptors, Antigen, T-Cell; C496618:VAV1 protein, human; D050721:Proto-Oncogene Proteins c-cbl; D051966:Phospholipase C gamma; C067419:CBL protein, human