T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain–containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor– and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.
Skip Nav Destination
Article navigation
19 April 1999
Article|
April 19 1999
SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
Anne Marie-Cardine,
Anne Marie-Cardine
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Henning Kirchgessner,
Henning Kirchgessner
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Eddy Bruyns,
Eddy Bruyns
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Andrej Shevchenko,
Andrej Shevchenko
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Matthias Mann,
Matthias Mann
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Frank Autschbach,
Frank Autschbach
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Sheldon Ratnofsky,
Sheldon Ratnofsky
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Stefan Meuer,
Stefan Meuer
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Burkhart Schraven
Burkhart Schraven
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Search for other works by this author on:
Anne Marie-Cardine
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Henning Kirchgessner
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Eddy Bruyns
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Andrej Shevchenko
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Matthias Mann
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Frank Autschbach
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Sheldon Ratnofsky
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Stefan Meuer
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Burkhart Schraven
From the *Immunomodulation Laboratory of the Institute for Immunology, and the ‡Institute for Pathology, University of Heidelberg, 69120 Heidelberg, Germany; the §Protein and Peptide Group, European Molecular Biology Laboratories, 69117 Heidelberg, Germany; and the ‖BASF Bioresearch Corporation, Worcester, Massachusetts 01605
Address correspondence to Burkhart Schraven, Institute for Immunology, Immunomodulation Laboratory, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Phone: 6221-56-4059; Fax: 6221-56-5541; E-mail: [email protected]
Anne Marie-Cardine is a recipient of a fellowship from the Training and Mobility of Researchers program of the European Community (ERBFMBICT950472). This work was supported in part by Deutsche Forschungsgemeinschaft grants SCHR/533/1-1 and SCHR/533/4-1 and by Sonderforschungsbereich (SFB) 405, projects A5 (to B. Schraven) and B9 (to F. Autschbach). The work in M. Mann's laboratory was partially supported by a grant from the German Technology Ministry (BMBF).
M. Mann's present address is Center of Experimental Bioinformatics, Odense University, Campusveij 55, DK-5230 Odense M, Denmark.
Anne Marie-Cardine and Henning Kirchgessner contributed equally to this work.
Received:
December 08 1998
Revision Received:
February 08 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (8): 1181–1194.
Article history
Received:
December 08 1998
Revision Received:
February 08 1999
Citation
Anne Marie-Cardine, Henning Kirchgessner, Eddy Bruyns, Andrej Shevchenko, Matthias Mann, Frank Autschbach, Sheldon Ratnofsky, Stefan Meuer, Burkhart Schraven; SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation . J Exp Med 19 April 1999; 189 (8): 1181–1194. doi: https://doi.org/10.1084/jem.189.8.1181
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
