Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways
Takata, M.; Sabe, H.; Hata, A.; Inazu, T.; Homma, Y.; Nukada, T.; Yamamura, H.; Kurosaki, T.
EMBO Journal 13(6): 1341-1349
1994
ISSN/ISBN: 0261-4189 PMID: 8137818 Document Number: 433515
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 (IP-3) generation and calcium mobilization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayed and slow Ca-2+ mobilization, despite the normal kinetics of IP-3 turnover. These results demonstrate that Syk mediates IP-3 generation, whereas Lyn regulates Ca-2+ mobilization through a process independent of IP-3 generation.