Activation of syk in an immature B cell line does not require lyn activity.

Abstract

BKS-2 is an immature B cell lymphoma that undergoes apoptotic cell death when signaled via its surface IgM receptor. To study the signaling components of surface IgM mediated apoptosis in B lymphoma cells, we generated mutants of BKS-2 that were resistant to anti-IgM induced apoptosis. One mutant cell line, 1.B5, did not undergo apoptotic cell death upon treatment with anti-IgM antibodies and also did not exhibit elevation of intracellular Ca2+ in response to cross-linking of surface IgM. This appeared to be due to a defect in protein tyrosine kinase (PTK) activity since fewer proteins were tyrosine phosphorylated in the mutant cells stimulated with anti-IgM when compared to wild type BKS-2. Subsequently, we showed that protein tyrosine kinases lyn and blk were inducibly tyrosine phosphorylated in the wild type BKS-2 but not in 1.B5 mutant cells in response to anti-IgM. Also the kinase activity of lyn was elevated in the wild type but not in mutant cells upon triggering through surface IgM. Furthermore, tyrosine phosphorylation of CD19, a known substrate of lyn, was inducible in anti-IgM stimulated BKS-2 cells but severely reduced in 1.B5 cells. In contrast, kinase activity of another src kinase, blk, was increased on anti-IgM stimulation in both wild type and mutant cells. Surprisingly, syk, a non-src protein tyrosine kinase important for surface IgM mediated signaling, was tyrosine phosphorylated in the lyn deficient mutant cells as well as in the wild type BKS-2 cells. Furthermore, anti-IgM induced increase in kinase activity of syk was similar in the mutant and wild type cells. Thus, in contrast to other studies that propose syk to be a downstream target of src family kinases, syk may act upstream of lyn in immature B cells. Consistent with a functional syk, its target, phospholipase gamma2 (PLC-gamma2) was normally tyrosine phosphorylated in mutant cells.

• Authors: S Muthukkumar, C Venkataraman, T Woods, S Bondada
• Journal: Molecular immunology (Mol Immunol) 1997 Aug-Sep Vol. 34 Issue 12-13 Pg. 865-75 ISSN: 0161-5890 [Print] England
• PMID: 9464522 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enzyme Precursors
• Intracellular Signaling Peptides and Proteins
• Receptors, Antigen, B-Cell
• Receptors, Fc
• immunoglobulin M receptor
• Tyrosine
• Protein-Tyrosine Kinases
• Syk Kinase
• Syk protein, mouse
• lyn protein-tyrosine kinase
• src-Family Kinases
• Calcium

Topics

• Animals
• Apoptosis
• B-Lymphocytes (enzymology)
• Calcium (metabolism)
• Cell Division
• Cell Line
• Enzyme Activation
• Enzyme Precursors (metabolism)
• Intracellular Signaling Peptides and Proteins
• Mice
• Mice, Inbred CBA
• Phosphorylation
• Protein-Tyrosine Kinases (metabolism)
• Receptors, Antigen, B-Cell (physiology)
• Receptors, Fc (metabolism)
• Signal Transduction
• Surface Properties
• Syk Kinase
• Tyrosine (metabolism)
• src-Family Kinases (metabolism)