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Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells
Author(s) -
Liu Yan,
Zhang Weiguo
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0208087
Subject(s) - signal transducing adaptor protein , grb2 , biology , transmembrane protein , microbiology and biotechnology , b cell receptor , transmembrane domain , breakpoint cluster region , b cell , signal transduction , receptor , antibody , biochemistry , immunology
Transmembrane adaptor proteins couple antigen receptor engagement to downstream signaling cascades in lymphocytes. One example of these proteins is the linker for activation of T cells (LAT), which plays an indispensable role in T cell activation and development. Here, we report identification of a new transmembrane adaptor molecule, namely growth factor receptor‐bound protein 2 (Grb2)‐binding adaptor protein, transmembrane (GAPT), which is expressed in B cells and myeloid cells. Similar to LAT, GAPT has an extracellular domain, a transmembrane domain, and a cytoplasmic tail with multiple Grb2‐binding motifs. In contrast to other transmembrane adaptor proteins, GAPT is not phosphorylated upon BCR ligation but associates with Grb2 constitutively through its proline‐rich region. Targeted disruption of the gapt gene in mice affects neither B cell development nor a nitrophenylacetyl‐specific antibody response. However, in the absence of GAPT, B cell proliferation after BCR cross‐linking is enhanced. In aged GAPT −/− mice, the number of marginal zone (MZ) B cells is increased, and other B cell subsets are normal. The serum concentrations of IgM, IgG2b, and IgG3 are also elevated in these mice. These data indicate that GAPT might play an important role in control of B cell activation and proper maintenance of MZ B cells.