Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways.
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.
Takata
M
M
Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, NY 10965.
Sabe
H
H
Hata
A
A
Inazu
T
T
Homma
Y
Y
Nukada
T
T
Yamamura
H
H
Kurosaki
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D004792:Enzyme Precursors / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D010716:Phosphatidylinositols / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D000072377:Syk Kinase; D019061:src-Family Kinases
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium