Home LiteratureArticle Details
PMID: 9705962 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation.

The Journal of experimental medicine ·Vol. 188 ·No. 4 ·1998-08-17 ·Pages 791-5

Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen PJ, Reth M

Abstract

The B cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin (Ig) molecule as antigen-binding subunit and the Ig-alpha/Ig-beta heterodimer as signaling subunit. BCR signal transduction involves activation of protein tyrosine kinases (PTKs) and phosphorylation of several proteins, only some of which have been identified. The phosphorylation of these proteins can be induced by exposure of B cells either to antigen or to the tyrosine phosphatase inhibitor pervanadate/H2O2. One of the earliest substrates in B cells is a 65-kD protein, which we identify here as a B cell adaptor protein. This protein, named SLP-65, is part of a signaling complex involving Grb-2 and Vav and shows homology to SLP-76, a signaling element of the T cell receptor. In pervanadate/H2O2-stimulated cells, SLP-65 becomes phosphorylated only upon expression of the BCR. These data suggest that SLP-65 is part of a BCR transducer complex.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals B-Lymphocytes/drug effects,metabolism Base Sequence Carrier Proteins Cell Cycle Proteins DNA, Complementary Enzyme Inhibitors/pharmacology GRB2 Adaptor Protein Humans Hydrogen Peroxide/pharmacology Immunoglobulin delta-Chains/metabolism Immunoglobulin mu-Chains/metabolism Molecular Sequence Data Phosphoproteins/genetics,metabolism Protein-Tyrosine Kinases/metabolism Proteins/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-vav Rabbits Receptors, Antigen, B-Cell/metabolism Signal Transduction Tumor Cells, Cultured Vanadates/pharmacology
Chemicals
Adaptor Proteins, Signal Transducing B cell linker protein Carrier Proteins Cell Cycle Proteins DNA, Complementary Enzyme Inhibitors GRB2 Adaptor Protein GRB2 protein, human Immunoglobulin delta-Chains Immunoglobulin mu-Chains Phosphoproteins Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-vav Receptors, Antigen, B-Cell VAV1 protein, human pervanadate Vanadates Hydrogen Peroxide Protein-Tyrosine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wienands J
Department for Molecular Immunology, Biology III, University of Freiburg, 79104 Freiburg, Germany. wienanands@immunbio.mpg.de
Schweikert J
Wollscheid B
Jumaa H
Nielsen P J
Reth M
References (26)
26 references, click to expand
  1. The structure of an antigenic determinant in a protein.
    Cell. 1984 Jul;37(3):767-78 PMID: 6204768
  2. Antigen receptor signaling gives lymphocytes a long life.
    Cell. 1997 Sep 19;90(6):971-3 PMID: 9323124
  3. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation.
    Cell. 1990 Feb 9;60(3):375-86 PMID: 2302733
  4. In vitro characterization of major ligands for Src homology 2 domains derived from protein tyrosine kinases, from the adaptor protein SHC and from GTPase-activating protein in Ramos B cells.
    Eur J Immunol. 1994 Aug;24(8):1799-807 PMID: 7519995
  5. A novel signaling molecule, p130, forms stable complexes in vivo with v-Crk and v-Src in a tyrosine phosphorylation-dependent manner.
    EMBO J. 1994 Aug 15;13(16):3748-56 PMID: 8070403
  6. Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells.
    J Biol Chem. 1995 Mar 31;270(13):7029-32 PMID: 7706237
  7. Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation.
    Immunity. 1996 Jun;4(6):593-602 PMID: 8673706
  8. Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production.
    J Exp Med. 1996 Apr 1;183(4):1937-43 PMID: 8666952
  9. Evidence for a preformed transducer complex organized by the B cell antigen receptor.
    Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7865-70 PMID: 8755568
  10. Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase.
    J Biol Chem. 1996 Sep 6;271(36):22225-30 PMID: 8703037
  11. Tyrosines 113, 128, and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity.
    J Immunol. 1996 Nov 1;157(9):3769-73 PMID: 8892604
  12. Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product.
    Nature. 1997 Jan 9;385(6612):169-72 PMID: 8990121
  13. Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking protein, Dok.
    Cell. 1997 Jan 24;88(2):205-11 PMID: 9008161
  14. p95vav associates with tyrosine-phosphorylated SLP-76 in antigen-stimulated T cells.
    J Exp Med. 1996 Sep 1;184(3):1161-6 PMID: 9064333
  15. Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases.
    J Biol Chem. 1997 May 2;272(18):11674-7 PMID: 9115214
  16. Initiation and processing of signals from the B cell antigen receptor.
    Annu Rev Immunol. 1997;15:453-79 PMID: 9143696
  17. Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK.
    Science. 1997 Jun 13;276(5319):1702-5 PMID: 9180081
  18. The complexity of signaling pathways activated by the BCR.
    Curr Opin Immunol. 1997 Jun;9(3):296-308 PMID: 9203421
  19. Molecular mechanisms in B cell antigen receptor signaling.
    Curr Opin Immunol. 1997 Jun;9(3):309-18 PMID: 9203415
  20. Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production.
    Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7493-8 PMID: 9207119
  21. A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade.
    Nature. 1997 Jul 17;388(6639):243-9 PMID: 9230432
  22. The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation.
    EMBO J. 1997 Aug 15;16(16):5077-85 PMID: 9305649
  23. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death.
    Cell. 1997 Sep 19;90(6):1073-83 PMID: 9323135
  24. Identification of two tyrosine phosphoproteins, pp70 and pp68, which interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen receptor activation.
    J Biol Chem. 1997 Oct 24;272(43):27362-8 PMID: 9341187
  25. Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development.
    Science. 1998 Jul 17;281(5375):416-9 PMID: 9665885
  26. v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas.
    Proc Natl Acad Sci U S A. 1989 Feb;86(4):1168-72 PMID: 2784003
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1998-08-17
Pages
791-5
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213353
Subset
IM
Databases
GENBANK
Y17159
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com