Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cγ1

Elektra J. Papadopoulos, David J. Fitzhugh, Christine Tkaczyk, Alasdair M. Gilfillan, Christopher Sassetti, Dean D. Metcalfe, Samuel T Hwang

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

One mechanism for transducing signals downstream of lymphocyte receptor activation involves the stable association between signaling proteins. To identify protein ligands of the signal activator phospholipase Cγ1 (PLCγ1), we screened T cell cDNA libraries with the PLCγ1-SH3 domain by the yeast two-hybrid assay. We observed association between the PLCγ1-SH3 domain and the human Ras guanine nucleotide exchange factor son-of-sevenless-2 (hSos2) through a proline-rich domain interaction. Stable and abundant hSos2/ PLCγ1 and hSosl/PLCγ1 complexes were observed in unstimulated T cells. The interaction between these enzymes was augmented following engagement of the T cell antigen receptor (TCR/CD3). The kinetics of protein complex enhancement correlated with TCR/CD3-induced tyrosine phosphorylation of PLCγ1; however; those PLCγ1 molecules in complex with hSos2 were non-phosphorylated after TCR/CD3 stimulation, in contrast to the phosphorylated PLCγ1 associated with the linker for activation of T cells, LAT. The Grb2 adapter protein was detected in complex with hSos/PLCγ1, suggesting a regulatory role for Grb2. SH3 domains from both Grb2 and PLCγ1, but not RasGAP, bound directly to hSos homologues. The SH2 domain from Grb2 formed an association with the hSos/PLCγ1 complex, which was enhanced following TCR/CD3 ligation. Together, the data suggest a mechanism for the son-of-sevenless and PLCγ1 signal transducing enzymes in recruitment to protein complexes with potentially differential signaling consequences in T lymphocytes.

Original languageEnglish (US)
Pages (from-to)2378-2387
Number of pages10
JournalEuropean Journal of Immunology
Volume30
Issue number8
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • Cellular activation
  • Phospholipase Cγ1
  • SH3
  • Signal transduction
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology

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