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| Subject Categories:
Signal Transduction
| Immunology
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The EMBO Journal
(2006) 25, 774–784, doi:10.1038/sj.emboj.7600978 Published online 9 February 2006
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Recruitment and activation of PLC 1 in T cells: a new insight into old domains |
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Alex Braiman, Mira Barda-Saad, Connie L Sommers and Lawrence E Samelson
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Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
To whom correspondence should be addressed
Lawrence E Samelson, Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 37, Room 2066, Bethesda, MD 20892-4254, USA. Tel.: +1 301 496 9683; Fax: +1 301 496 8479; E-mail: samelson@helix.nih.gov
Received 25 August 2005; Accepted 9 January 2006; Published online 9 February 2006.
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| Abstract |
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Engagement of the T-cell antigen receptor leads to recruitment of phospholipase C 1 (PLC 1) to the LAT-nucleated signaling complex and to PLC 1 activation in a tyrosine phosphorylation-dependent manner. The mechanism of PLC 1 recruitment and the role of PLC 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 1 is necessary but not sufficient for its recruitment. Either the SH3 or C-terminal SH2 domain of PLC 1, with the participation of Vav1, c-Cbl and Slp76, are required to stabilize PLC 1 recruitment. All three PLC 1 SH domains are required for phosphorylation of PLC 1 Y783, which is critical for enzyme activation. These novel findings entailed revision of the currently accepted model of PLC 1 recruitment and activation in T lymphocytes. |
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| Keywords: calcium, confocal microscopy, FRET, protein–protein interaction, TCR |
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