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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3 May 1999
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May 03 1999
Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT
Hiroshi Asada,
Hiroshi Asada
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Naoto Ishii,
Naoto Ishii
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Yoshiteru Sasaki,
Yoshiteru Sasaki
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Kazuhiro Endo,
Kazuhiro Endo
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Hirotake Kasai,
Hirotake Kasai
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Nobuyuki Tanaka,
Nobuyuki Tanaka
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Toshikazu Takeshita,
Toshikazu Takeshita
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Shigeru Tsuchiya,
Shigeru Tsuchiya
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Tasuke Konno,
Tasuke Konno
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Kazuo Sugamura
Kazuo Sugamura
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
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Hiroshi Asada
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Naoto Ishii
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Yoshiteru Sasaki
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Kazuhiro Endo
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Hirotake Kasai
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Nobuyuki Tanaka
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Toshikazu Takeshita
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Shigeru Tsuchiya
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Tasuke Konno
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Kazuo Sugamura
From the *Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan; the ‡Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; the §Research Institute, Miyagi Cancer Center, Natori 981-1293, Japan; and ‖Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, Tokyo 101-0062, Japan
Address correspondence to Kazuo Sugamura, Department of Microbiology and Immunology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Phone: 81-22-717-8096; Fax: 81-22-717-8097; E-mail: [email protected]
Received:
October 19 1998
Revision Received:
March 01 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (9): 1383–1390.
Article history
Received:
October 19 1998
Revision Received:
March 01 1999
Citation
Hiroshi Asada, Naoto Ishii, Yoshiteru Sasaki, Kazuhiro Endo, Hirotake Kasai, Nobuyuki Tanaka, Toshikazu Takeshita, Shigeru Tsuchiya, Tasuke Konno, Kazuo Sugamura; Grf40, A Novel Grb2 Family Member, Is Involved in T Cell Signaling through Interaction with SLP-76 and LAT . J Exp Med 3 May 1999; 189 (9): 1383–1390. doi: https://doi.org/10.1084/jem.189.9.1383
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