TY - JOUR
T1 - Grf40, a novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT
AU - Asada, Hiroshi
AU - Ishii, Naoto
AU - Sasaki, Yoshiteru
AU - Endo, Kazuhiro
AU - Kasai, Hirotake
AU - Tanaka, Nobuyuki
AU - Takeshita, Toshikazu
AU - Tsuchiya, Shigeru
AU - Konno, Tasuke
AU - Sugamura, Kazuo
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/5/3
Y1 - 1999/5/3
N2 - 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.
AB - 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.
KW - Grb2 family
KW - Nuclear factor of activated T cells
KW - SLP-76
KW - T cell receptor signaling
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U2 - 10.1084/jem.189.9.1383
DO - 10.1084/jem.189.9.1383
M3 - Article
C2 - 10224278
AN - SCOPUS:0033519283
VL - 189
SP - 1383
EP - 1390
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 9
ER -