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Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.

Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Research Abstract Details 

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  • Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Abstract Text:

    leonard l dragoneLeonard L Dragone,margaret d myersMargaret D Myers,carmen whiteCarmen White,shyam gadwalShyam Gadwal,tomasz sosinowskiTomasz Sosinowski,hua guHua Gu,arthur weissArthur Weiss,

    Src-like adaptor protein (SLAP) and c-Cbl recently have been shown to cooperate in regulating T cell receptor (TCR) levels in developing T cells. SLAP also is expressed in developing B cells, and its deficiency leads to alterations in B cell receptor (BCR) levels and B cell development. Hence, we hypothesized that SLAP and c-Cbl may cooperate during B cell development to regulate BCR levels. In mice deficient in both SLAP and c-Cbl, we found that B cell development is altered, suggesting that they function through intersecting pathways. To study the mechanism by which SLAP and c-Cbl alter BCR levels, we coexpressed them in a mature mouse B cell line (Bal-17). First we determined that SLAP associates with proximal components of the BCR complex after stimulation and internalization. Coexpression of SLAP and c-Cbl in Bal-17 led to decreased surface and total BCR levels. This decrease in BCR levels depended on intact Src homology 2 (SH2) and C-terminal domains of SLAP. In addition, a mutation in the SH2 domain of SLAP blocked its colocalization with c-Cbl and the BCR complex, whereas deletion of the C terminus did not affect its localization. Last, coexpression of SLAP and c-Cbl altered BCR complex recycling. This alteration in BCR complex recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2 and C-terminal domains of SLAP. These data suggest that SLAP has a conserved function in B and T cells by adapting c-Cbl to the antigen-receptor complex and targeting it for degradation.

    Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Publishing Authors By Initials

    ll dragoneLL Dragone,md myersMD Myers,c whiteC White,s gadwalS Gadwal,t sosinowskiT Sosinowski,h guH Gu,a weissA Weiss,

    For similar proteins: blood proteins: immunoproteins: immunoglobulins: receptors, antigen, b-cell research abstracts see: proteins: blood proteins: immunoproteins: immunoglobulins: receptors, antigen, b-cell research

    PUBMED ID PMID:

    MEDLINE DATE:

    Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Proceedings of the National Academy of Sciences of

    VOLUME: 103

    Page Numbers: 18202-7

    Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

    ISSN: 0027-8424

    DAY: 16

    MONTH: 11

    YEAR: 2006

    Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7505876

    Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Keywords Mesh Terms:

    KEYWORDS: Receptors, Antigen, B-Cell

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner. Information

    Substance Name: Proto-Oncogene Proteins c-cbl

    Registry Number: EC 6.3.2.-

    Grant and Affiliation Information for Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner.

    AFFILIATION: Division of Pediatric Immunology/Rheumatology, Department of Pediatrics, University of California, San Francisco, CA 94143, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCI

    GRANT: CA72531

    ACRONYM: CA

    MEDLINETA: Proc Natl Acad Sci U S A

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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