Publication Date:
1998-01-15
Description:
In this report, we show that the Src family nonreceptor protein tyrosine kinase (PTK) Lyn associates with aggregated IgA Fc receptor (FcαR) in the monocytic cell line THP-1. Receptor aggregation and subsequent immunoprecipitation of receptor complexes with huIgA adsorbed to nitrocellulose particles shows that Lyn associates with FcαR by a mechanism sensitive to short treatment with the Src family-selective inhibitor PP1. However, interaction of Lyn with IgG Fc receptor (FcγR) in THP-1 cells was unaffected by short treatment with the PTK inhibitor. Cross-linking of FcαR induced tyrosine phosphorylation of several cellular proteins, including p72Syk, which appears to be a major target of early PTK activity. Unexpectedly, in vitro kinase assays showed that FcαR aggregation-induced tyrosine phosphorylation of Syk did not result in upregulation of Syk activity. Despite the lack of enhanced Syk kinase activity, downstream signaling after FcαR cross-linking was functional and induced the release of significant amounts of interleukin-1 receptor antagonist and interleukin-8. The induction of cytokine release was completely blocked by PP1, thus confirming the biological significance of the association of Lyn with aggregated FcαR. Our data show that early signal transduction after FcαR cross-linking as well as FcαR-mediated activation of cellular effector functions depends on Src family kinase activity. The Src-family PTK involved in FcαR-mediated tyrosine phosphorylation appears to be Lyn, which coprecipitated with aggregated FcαR complexes.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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