Physical and functional association of Fc alpha R with protein tyrosine kinase Lyn.
In this report, we show that the Src family nonreceptor protein tyrosine kinase (PTK) Lyn associates with aggregated IgA Fc receptor (Fc alpha R) 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 Fc alpha R by a mechanism sensitive to short treatment with the Src family-selective inhibitor PP1. However, interaction of Lyn with IgG Fc receptor (Fc gamma R) in THP-1 cells was unaffected by short treatment with the PTK inhibitor. Cross-linking of Fc alpha R 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 Fc alpha R 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 Fc alpha R 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 Fc alpha R. Our data show that early signal transduction after Fc alpha R cross-linking as well as Fc alpha R-mediated activation of cellular effector functions depends on Src family kinase activity. The Src-family PTK involved in Fc alpha R-mediated tyrosine phosphorylation appears to be Lyn, which coprecipitated with aggregated Fc alpha R complexes.
Gulle
H
H
Institute of Immunology, University of Vienna, Austria.
Samstag
A
A
Eibl
M M
MM
Wolf
H M
HM
D002460:Cell Line; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation; D011961:Receptors, Fc / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism*
D011961:Receptors, Fc; D014443:Tyrosine; D019061:src-Family Kinases