4.5 Article

Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells

期刊

JOURNAL OF LEUKOCYTE BIOLOGY
卷 84, 期 3, 页码 842-851

出版社

FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0208087

关键词

marginal zone B cells; BCR signaling; B cell proliferation

资金

  1. National Institutes of Heath [AI048674, AI056156]

向作者/读者索取更多资源

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 prolinerich 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.

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