First Author | Fujimoto M | Year | 2000 |
Journal | Immunity | Volume | 13 |
Issue | 1 | Pages | 47-57 |
PubMed ID | 10933394 | Mgi Jnum | J:112423 |
Mgi Id | MGI:3656321 | Doi | 10.1016/s1074-7613(00)00007-8 |
Citation | Fujimoto M, et al. (2000) CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification. Immunity 13(1):47-57 |
abstractText | CD19 regulates constitutive and antigen receptor-induced signaling thresholds in B lymphocytes through its unique cytoplasmic domain. Herein, we demonstrate a novel molecular mechanism where interactions between CD19 and Lyn amplify basal and antigen receptor-induced Src family kinase activation. Lyn expression was required for CD19 tyrosine phosphorylation in primary B cells. Experiments with purified proteins demonstrated that CD19-Y513 was Lyn's initial phosphorylation and binding site. This led to processive phosphorylation of CD19-Y482, which recruited a second Lyn molecule, allowing for transphosphorylation and amplification of Lyn activation. In vivo, CD19 deficiency impaired, and CD19 overexpression enhanced, Lyn kinase activity. Thus, CD19 functions as a specialized adapter protein for the amplification of Src family kinases that is crucial for intrinsic and antigen receptor-induced signal transduction. |