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Lipopolysaccharide‐induced cytokine production in human monocytes: Role of tyrosine phosphorylation in transmembrane signal transduction
Author(s) -
Beaty Christopher D.,
Franklin Terry L.,
Uehara Yoshimasa,
Wilson Christopher B.
Publication year - 1994
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830240606
Subject(s) - protein tyrosine phosphatase , lyn , tyrosine phosphorylation , proto oncogene tyrosine protein kinase src , biology , tyrosine kinase , signal transduction , phosphorylation , microbiology and biotechnology , tyrosine , biochemistry
Abstract The signal transduction events that follow the binding of lipopolysaccharide (LPS) to the macrophage cell surface are not well defined. In the current studies LPS was found to induce alterations in phosphorylation of monocyte proteins on tyrosine. Herbimycin A and genistein, inhibitors of tyrosine kinases, markedly attenuated LPS‐induced tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) protein and mRNA production. Reciprocally, the tyrosine phosphatase inhibitor sodium orthovanadate enhanced LPS‐induced production of TNF‐α. LPS induced a concentration‐dependent increase in tyrosine phosphorylation of several proteins, which paralleled and preceded the onset of LPS‐induced TNF‐α production. LPS stimulation had different but reproducible effects on three members of the src family of tyrosine kinases. Both Hck and Lyn kinase activity increased before the onset of TNF‐α production, consistent with their participation in the observed LPS‐induced tyrosine phosphoprotein accumulation. In contrast, Yes kinase activity was not affected. These observations were made at concentrations of LPS that required serum rich in LPS‐binding protein and the monocyte surface antigen CD14 for TNF‐α production. These data indicate that tyrosine kinases and phosphatases are involved in the signal transduction cascade by which LPS induces production of TNF‐α and IL‐6 by human monocytes, and suggest that Lyn and Hck are candidate participants in this process.