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

Immunity. 2000 Jul;13(1):47-57. doi: 10.1016/s1074-7613(00)00007-8.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD19 / genetics
  • Antigens, CD19 / metabolism*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Binding Sites
  • Cattle
  • Cell Cycle Proteins*
  • Enzyme Activation
  • Gene Expression
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-vav
  • Substrate Specificity
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*


  • Antigens, CD19
  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Vav1 protein, mouse
  • Phosphatidylinositol 3-Kinases
  • lyn protein-tyrosine kinase
  • src-Family Kinases