| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Fuchu, Tokyo, Japan
Src homology region 2 (SH2) domain-containing phosphatase-1 (SHP-1) is a cytosolic protein tyrosine phosphatase containing two SH2 domains in its NH2 terminus. That immunological abnormalities of the motheaten and viable motheaten mice are caused by mutations in the gene encoding SHP-1 indicates that SHP-1 plays important roles in lymphocyte differentiation, proliferation, and activation. To elucidate molecular mechanisms by which SHP-1 regulates BCR-mediated signal transduction, we determined SHP-1 substrates in B cells using the substrate-trapping approach. When the phosphatase activity-deficient form of SHP-1, in which the catalytic center cysteine (C453) was replaced with serine (SHP-1-C/S), was introduced in WEHI-231 cells, tyrosine phosphorylation of a protein of about 70 kDa was strongly enhanced. Immunoprecipitation and Western blot analyses revealed that this protein is the B cell linker protein (BLNK), also named SH2 domain leukocyte protein of 65 kDa, and that upon tyrosine phosphorylation BLNK binds to SHP-1-C/S in vitro. In vitro kinase assays demonstrated that hyperphosphorylation of BLNK in SHP-1-C/S-expressing cells was not due to enhanced activity of Lyn or Syk. Furthermore, BCR-induced activation of c-Jun NH2-terminal kinase was shown to be significantly enhanced in SHP-1-C/S transfectants. Taken collectively, our results suggest that BLNK is a physiological substrate of SHP-1 in B cells and that SHP-1 selectively regulates c-Jun NH2-terminal kinase activation.
This article has been cited by other articles:
|
|
 |
|
  E. O. Lobo, Z. Zhang, and J. E. Shively Pivotal Advance: CEACAM1 is a negative coreceptor for the B cell receptor and promotes CD19-mediated adhesion of B cells in a PI3K-dependent manner J. Leukoc. Biol., August 1, 2009; 86(2): 205 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Vendel, J. Calemine-Fenaux, A. Izrael-Tomasevic, V. Chauhan, D. Arnott, and D. L. Eaton B and T Lymphocyte Attenuator Regulates B Cell Receptor Signaling by Targeting Syk and BLNK J. Immunol., February 1, 2009; 182(3): 1509 - 1517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakata, T. Yoshimaru, Y. Suzuki, T. Inoue, C. Ra, H. Yakura, and K. Mizuno Positive and Negative Regulation of High Affinity IgE Receptor Signaling by Src Homology Region 2 Domain-Containing Phosphatase 1 J. Immunol., October 15, 2008; 181(8): 5414 - 5424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. S. Cho, S. Y. Oh, and Z. Zhu Tyrosine Phosphatase SHP-1 in Oxidative Stress and Development of Allergic Airway Inflammation Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 412 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ozawa, K. Nakata, K. Mizuno, and H. Yakura Negative autoregulation of Src homology region 2-domain-containing phosphatase-1 in rat basophilic leukemia-2H3 cells Int. Immunol., September 1, 2007; 19(9): 1049 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ogimoto, G. Ichinowatari, N. Watanabe, N. Tada, K. Mizuno, and H. Yakura Impairment of B cell receptor-mediated Ca2+ influx, activation of mitogen-activated protein kinases and growth inhibition in CD72-deficient BAL-17 cells Int. Immunol., July 1, 2004; 16(7): 971 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chen, H. Iijima, T. Nagaishi, A. Nakajima, S. Russell, R. Raychowdhury, V. Morales, C. E. Rudd, N. Utku, and R. S. Blumberg Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 Isoforms Alternatively Inhibit and Costimulate Human T Cell Function J. Immunol., March 15, 2004; 172(6): 3535 - 3543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hokazono, T. Adachi, M. Wabl, N. Tada, T. Amagasa, and T. Tsubata Inhibitory Coreceptors Activated by Antigens But Not by Anti-Ig Heavy Chain Antibodies Install Requirement of Costimulation Through CD40 for Survival and Proliferation of B Cells J. Immunol., August 15, 2003; 171(4): 1835 - 1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Baba, N. Fusaki, N. Shinya, A. Iwamatsu, and N. Hozumi Actin Tyrosine Dephosphorylation by the Src Homology 1-Containing Protein Tyrosine Phosphatase Is Essential for Actin Depolymerization After Membrane IgM Cross-Linking J. Immunol., April 1, 2003; 170(7): 3762 - 3768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Hibbs, K. W. Harder, J. Armes, N. Kountouri, C. Quilici, F. Casagranda, A. R. Dunn, and D. M. Tarlinton Sustained Activation of Lyn Tyrosine Kinase In Vivo Leads to Autoimmunity J. Exp. Med., December 16, 2002; 196(12): 1593 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Nielsen and R. G. Q. Leslie Complement's participation in acquired immunity J. Leukoc. Biol., August 1, 2002; 72(2): 249 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Mizuno, Y. Tagawa, K. Mitomo, N. Watanabe, T. Katagiri, M. Ogimoto, and H. Yakura Src Homology Region 2 Domain-Containing Phosphatase 1 Positively Regulates B Cell Receptor-Induced Apoptosis by Modulating Association of B Cell Linker Protein with Nck and Activation of c-Jun NH2-Terminal Kinase J. Immunol., July 15, 2002; 169(2): 778 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Gary-Gouy, J. Harriague, A. Dalloul, E. Donnadieu, and G. Bismuth CD5-Negative Regulation of B Cell Receptor Signaling Pathways Originates from Tyrosine Residue Y429 Outside an Immunoreceptor Tyrosine-Based Inhibitory Motif J. Immunol., January 1, 2002; 168(1): 232 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Adachi, J. Wienands, C. Wakabayashi, H. Yakura, M. Reth, and T. Tsubata SHP-1 Requires Inhibitory Co-receptors to Down-modulate B Cell Antigen Receptor-mediated Phosphorylation of Cellular Substrates J. Biol. Chem., July 6, 2001; 276(28): 26648 - 26655. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
