title: Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways.
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.
authors.affiliation: Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, NY 10965.
authors.forename: M
authors.initials: M
authors.lastname: Takata
authors.forename: H
authors.initials: H
authors.lastname: Sabe
authors.forename: A
authors.initials: A
authors.lastname: Hata
authors.forename: T
authors.initials: T
authors.lastname: Inazu
authors.forename: Y
authors.initials: Y
authors.lastname: Homma
authors.forename: T
authors.initials: T
authors.lastname: Nukada
authors.forename: H
authors.initials: H
authors.lastname: Yamamura
authors.forename: T
authors.initials: T
authors.lastname: Kurosaki
mesh_terms: 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
chemical_list: 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