Editors' ChoiceImmunology

Signal Amplification

Science's STKE  25 Jul 2000:
Vol. 2000, Issue 42, pp. tw8
DOI: 10.1126/stke.2000.42.tw8

CD19 is a transmembrane protein that is part of a complex that controls signaling through the B cell receptor (BCR). Knockout of CD19 results in impaired B cell signaling, and overexpression of CD19 enhances B cell signaling. Fujimoto et al. propose a mechanism by which CD19 is phosphorylated by and subsequently recruits two Lyn tyrosine kinases, which tandemly bind the cytoplasmic tail of CD19, leading to amplification of Lyn activity. Experiments were performed in cells lacking Lyn or CD19; they demonstrated that CD19 is phosphorylated by Lyn in vivo and that in CD19-deficient cells Lyn and Vav phosphorylation in response to BCR activation was impaired, thus establishing interactions among these proteins. Using in vitro assays with glutathione S-transferase fusion proteins and CD19 peptides, the authors mapped the tyrosine residues phosphorylated by Lyn and demonstrated that phosphorylation of two of these residues was essential for stimulating Lyn activity for a target substrate in vitro. Finally, biotinylated Lyn and radiolabeled Lyn were mixed with CD19 in an in vitro kinase assay and radiolabeled Lyn coprecipitated with biotinylated Lyn. This interaction was dependent on the presence of both of the essential CD19 tyrosine residues. The authors suggest that CD19 acts as an adaptor to bring two pairs of Lyn molecules together to promote BCR signaling.

Fujimoto, M., Fujimoto, Y., Poe, J.C., Jansen, P.J., Lowell, C.A., DeFranco, A.L., and Tedder, T.F. (2000) CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification. Immunity 13: 47-57. [Online Journal]