Surface immunoglobulin crosslinking activates a tyrosine kinase pathway in B cells that is independent of protein kinase C.
Proc Natl Acad Sci U S A
; 88(4): 1311-4, 1991 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-1705033
ABSTRACT
It has been found that the principal biochemical pathway activated in B cells stimulated by antigen- or anti-immunoglobulin-mediated crosslinking of surface immunoglobulin is that resulting in hydrolysis of phosphatidylinositol bisphosphate with generation of diacylglycerol and inositol trisphosphate. Recent evidence suggests that surface immunoglobulin-mediated B-cell activation can proceed without detectable increases in the concentration of either diacylglycerol or intracellular Ca2+ concentration, implicating involvement of other non-protein-kinase-C/Ca2(+)-dependent signal-transduction pathways. Therefore, we sought evidence for activation of a signaling pathway that is associated with growth regulation in other cell types--i.e., the protein-tyrosine kinases. We now show that crosslinking of membrane immunoglobulin by mitogenic antibodies leads to rapid tyrosine phosphorylation of several cellular substrates, consistent with the induction of a tyrosine kinase activity. This increase in tyrosine phosphorylation is weakly (if at all) stimulated by other B-cell mitogens, including phorbol esters and ionophores, and does not require the presence of detectable protein kinase C. Furthermore, inhibition of anti-immunoglobulin-stimulated phosphatidylinositol bisphosphate hydrolysis does not inhibit activation of this tyrosine kinase-dependent pathway. These findings suggest that occupancy of the membrane immunoglobulin receptor may induce multiple pathways of activation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C
/
Protein-Tyrosine Kinases
/
B-Lymphocytes
/
Receptors, Antigen, B-Cell
/
Cross-Linking Reagents
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
1991
Document type:
Article