Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ligation of the Ag receptor on B cells is associated with a rapid increase in phosphorylation on tyrosine residues of multiple substrates. One of the substrates is the phosphoinositide-specific phospholipase C-gamma 1. Because activation of phospholipase C-gamma 1 seems to be dependent on tyrosine phosphorylation, it is assumed that the two signaling pathways, phosphatidylinositol turnover and tyrosine phosphorylation, might be linked. However, since the Ag receptor does not possess a kinase domain, it remains unclear how these signaling pathways are regulated by the Ag receptor. Previous studies have proposed the existence of a receptor-coupled G protein that regulates inositol phosphate production in B cells. We confirm that phosphoinositide turnover is regulated by a pertussis toxin (PT)-sensitive G protein, most probably by controlling phosphorylation of phospholipase C-gamma 1. We show that treatment of permeabilized B cells with a nonhydrolyzable GTP analogue guanosine 5'-[3-thio]triphosphate induced an increase in tyrosine phosphorylation of multiple substrates that are identical to the proteins phosphorylated after anti-IgM stimulation. Furthermore, binding of the inactive form of G proteins with guanosine 5'-[2-thio]-triphosphate blocked anti-IgM induced tyrosine phosphorylation in permeabilized B cells. The results indicate that an Ag receptor-coupled G protein controls protein tyrosine kinase activity. We show that this G protein is sensitive to PT because tyrosine phosphorylation mediated by the Ag receptor was inhibited by this toxin in a concentration-dependent manner. Similar concentrations of PT also blocked tyrosine phosphorylation on phospholipase C-gamma 1 and generation of inositol phosphates. Preincubation of intact B cells with PT resulted in inhibition of c-fos mRNA expression and DNA synthesis in anti-IgM stimulated B cells, indicating that post-transcriptional events are also controlled by the Ag-receptor coupled G protein. We conclude that Ag receptor-associated protein tyrosine kinase activity is regulated by a G protein. This PT-sensitive G protein also regulates phosphorylation and activation of phospholipase C-gamma 1 as well as later events in B cell activation such as c-fos mRNA expression and proliferation.
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PMID:Antigen receptor-mediated protein tyrosine kinase activity is regulated by a pertussis toxin-sensitive G protein. 137 48

In this study, we have examined the relationship between epidermal growth factor (EGF)-induced tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and its translocation from the cytosol to the Triton X-100-insoluble cytoskeleton fraction in rat hepatocytes. The translocation of PLC-gamma 1 was specific for EGF stimulation, because a similar effect was not observed with insulin or vasopressin. EGF caused a transient increase of PLC activity in the cytoskeleton fraction which could be abolished by immunoprecipitating PLC-gamma 1. Tyrosine phosphorylated PLC-gamma 1 was seen only in the cytoskeleton fraction, suggesting that tyrosine phosphorylation is required for PLC-gamma 1 translocation to the cytoskeleton. This process may involve binding of PLC-gamma 1 to actin filaments, since actin was immunoprecipitated together with PLC-gamma 1 in the cytoskeleton after EGF treatment. EGF-induced translocation of PLC-gamma 1 to the cytoskeleton was not inhibited by pertussis toxin, but Gi alpha was translocated in an EGF-dependent manner, suggesting that the interaction of PLC-gamma 1 with its activated Gi-protein is downstream from both PLC-gamma 1 tyrosine phosphorylation and its translocation to the cytoskeleton. Taken together, the present studies indicate that EGF-induced tyrosine phosphorylation of PLC-gamma 1, its association with the cytoskeleton, and its interaction with activated Gi alpha protein are all obligatory for PLC-gamma 1 activation in hepatocytes.
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PMID:Epidermal growth factor-induced activation and translocation of phospholipase C-gamma 1 to the cytoskeleton in rat hepatocytes. 812 25