Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells.
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.
Liu
Yan
Y
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Zhang
Weiguo
W
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D049109:Cell Proliferation; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051380:GRB2 Adaptor Protein / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D047468:Immunoprecipitation; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C110810:LAT protein, human; C419196:LAT2 protein, human; C469997:LAX1 protein, human; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell