Grf40, a novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT

Hiroshi Asada, Naoto Ishii, Yoshiteru Sasaki, Kazuhiro Endo, Hirotake Kasai, Nobuyuki Tanaka, Toshikazu Takeshita, Shigeru Tsuchiya, Tasuke Konno, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

130 Citations (Scopus)

Abstract

We molecularly cloned a new Grb2 family member, named Grf40, containing the common SH3-SH2-SH3 motif. Expression of Grf40 is predominant in hematopoietic cells, particularly T cells. Grf40 binds to the SH2 domain- containing leukocyte protein of 76 kD (SLP-76) via its SH3 domain more tightly than Grb2. Incidentally, Grf40 binds to linker for activation of T cells (LAT) possibly via its SH2 domain. Overexpression of wild-type Grf40 in Jurkat cells induced a significant increase of SLP-76-dependent interleukin (IL)-2 promoter and nuclear factor of activated T cell (NF-AT) activation upon T cell receptor (TCR) stimulation, whereas the COOH-terminal SH3- deleted Grf40 mutant lacked any recognizable increase in IL-2 promoter activity. Furthermore, the SH2-deleted Grf40 mutant led to a marked inhibition of these regulatory activities, the effect of which is apparently stronger than that of the SH2-deleted Grb2 mutant. Our data suggest that Grf40 is an adaptor molecule involved in TCR-mediated signaling through a more efficient interaction than Grb2 with SLP-76 and LAT.

Original languageEnglish
Pages (from-to)1383-1390
Number of pages8
JournalJournal of Experimental Medicine
Volume189
Issue number9
DOIs
Publication statusPublished - 1999 May 3

Keywords

  • Grb2 family
  • Nuclear factor of activated T cells
  • SLP-76
  • T cell receptor signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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