CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes through processive amplification.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Fujimoto, M; Fujimoto, Y; Poe, JC; Jansen, PJ; Lowell, CA; DeFranco, AL; Tedder, TF

Published Date

  • July 2000

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 47 - 57

PubMed ID

  • 10933394

International Standard Serial Number (ISSN)

  • 1074-7613

Language

  • eng

Conference Location

  • United States