Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways

EMBO J. 1994 Mar 15;13(6):1341-9.

Abstract

Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation on a number of proteins and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. The BCR associates with two classes of tyrosine kinase: Src-family kinase (Lyn, Fyn, Blk or Lck) and Syk kinase. To dissect the functional roles of these two types of kinase in BCR signaling, lyn-negative and syk-negative B cell lines were established. Syk-deficient B cells abolished the tyrosine phosphorylation of phospholipase C-gamma 2, resulting in the loss of both inositol 1,4,5-trisphosphate (IP3) generation and calcium mobilization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayed and slow Ca2+ mobilization, despite the normal kinetics of IP3 turnover. These results demonstrate that Syk mediates IP3 generation, whereas Lyn regulates Ca2+ mobilization through a process independent of IP3 generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cells, Cultured
  • Chickens
  • Enzyme Precursors / metabolism*
  • Inositol 1,4,5-Trisphosphate / biosynthesis
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Phosphatidylinositols / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, B-Cell / metabolism*
  • Syk Kinase
  • src-Family Kinases*

Substances

  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Phosphatidylinositols
  • Receptors, Antigen, B-Cell
  • Inositol 1,4,5-Trisphosphate
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • Calcium