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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Base Sequence, Binding Sites, COS Cells, Carrier Proteins, Cell Line, DNA, Complementary, DNA-Binding Proteins, GRB2 Adaptor Protein, Hela Cells, Humans, Interleukin-2, Jurkat Cells, Membrane Proteins, Molecular Sequence Data, NFATC Transcription Factors, Nuclear Proteins, Phosphoproteins, Proteins, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Transcription Factors, src Homology Domains
J. Exp. Med.
Date: May. 03, 1999
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