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

Yan Liu and Weiguo Zhang¹

Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA

¹ Correspondence: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA. E-mail: zhang033{at}mc.duke.edu

Transmembrane adaptor proteins couple antigen receptor engagementto downstream signaling cascades in lymphocytes. One exampleof 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 adaptormolecule, namely growth factor receptor-bound protein 2 (Grb2)-bindingadaptor protein, transmembrane (GAPT), which is expressed inB cells and myeloid cells. Similar to LAT, GAPT has an extracellulardomain, a transmembrane domain, and a cytoplasmic tail withmultiple Grb2-binding motifs. In contrast to other transmembraneadaptor proteins, GAPT is not phosphorylated upon BCR ligationbut associates with Grb2 constitutively through its proline-richregion. Targeted disruption of the gapt gene in mice affectsneither B cell development nor a nitrophenylacetyl-specificantibody response. However, in the absence of GAPT, B cell proliferationafter 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 concentrationsof IgM, IgG2b, and IgG3 are also elevated in these mice. Thesedata indicate that GAPT might play an important role in controlof B cell activation and proper maintenance of MZ B cells.

Key Words: marginal zone B cells • BCR signaling • B cell proliferation