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 Grb...

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Autores principales: Asada, Hiroshi, Ishii, Naoto, Sasaki, Yoshiteru, Endo, Kazuhiro, Kasai, Hirotake, Tanaka, Nobuyuki, Takeshita, Toshikazu, Tsuchiya, Shigeru, Konno, Tasuke, Sugamura, Kazuo
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193052/
https://www.ncbi.nlm.nih.gov/pubmed/10224278
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author Asada, Hiroshi
Ishii, Naoto
Sasaki, Yoshiteru
Endo, Kazuhiro
Kasai, Hirotake
Tanaka, Nobuyuki
Takeshita, Toshikazu
Tsuchiya, Shigeru
Konno, Tasuke
Sugamura, Kazuo
author_facet Asada, Hiroshi
Ishii, Naoto
Sasaki, Yoshiteru
Endo, Kazuhiro
Kasai, Hirotake
Tanaka, Nobuyuki
Takeshita, Toshikazu
Tsuchiya, Shigeru
Konno, Tasuke
Sugamura, Kazuo
author_sort Asada, Hiroshi
collection PubMed
description 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.
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spelling pubmed-21930522008-04-16 Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT Asada, Hiroshi Ishii, Naoto Sasaki, Yoshiteru Endo, Kazuhiro Kasai, Hirotake Tanaka, Nobuyuki Takeshita, Toshikazu Tsuchiya, Shigeru Konno, Tasuke Sugamura, Kazuo J Exp Med Articles 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. The Rockefeller University Press 1999-05-03 /pmc/articles/PMC2193052/ /pubmed/10224278 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Asada, Hiroshi
Ishii, Naoto
Sasaki, Yoshiteru
Endo, Kazuhiro
Kasai, Hirotake
Tanaka, Nobuyuki
Takeshita, Toshikazu
Tsuchiya, Shigeru
Konno, Tasuke
Sugamura, Kazuo
Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT
title Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT
title_full Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT
title_fullStr Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT
title_full_unstemmed Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT
title_short Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT
title_sort grf40, a novel grb2 family member, is involved in t cell signaling through interaction with slp-76 and lat
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193052/
https://www.ncbi.nlm.nih.gov/pubmed/10224278
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