IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells.

ABSTRACT: Interferon-induced transmembrane protein 3 (IFITM3) has previously been identified as an endosomal protein that blocks viral infection^1-3. Here we studied clinical cohorts of patients with B cell leukaemia and lymphoma, and identified IFITM3 as a strong predictor of poor outcome. In normal resting B cells, IFITM3 was minimally expressed and mainly localized in endosomes. However, engagement of the B cell receptor (BCR) induced both expression of IFITM3 and phosphorylation of this protein at Tyr20, which resulted in the accumulation of IFITM3 at the cell surface. In B cell leukaemia, oncogenic kinases phosphorylate IFITM3 at Tyr20, which causes constitutive localization of this protein at the plasma membrane. In a mouse model, Ifitm3^-/- naive B cells developed in norma

SUBMITTER: Lee J 

PROVIDER: S-EPMC8087162 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature