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. 1995 May;1(4):428–435.

LPS and Taxol activate Lyn kinase autophosphorylation in Lps(n), but not in Lpsd), macrophages.

B E Henricson 1, J M Carboni 1, A L Burkhardt 1, S N Vogel 1
PMCID: PMC2230002  PMID: 8521300

Abstract

BACKGROUND: The anti-tumor agent, Taxol, has been shown in murine macrophages to stimulate tumor necrosis factor (TNF), modulate TNF receptors, induce a large panel of immediate-early genes, and induce protein tyrosine phosphorylation indistinguishably from LPS. These data, coupled with the finding that lipid A antagonists block Taxol-induced stimulation, support the hypothesis that these two structurally unrelated compounds activate a common, receptor-associated signaling apparatus. A very early event in LPS signaling of human monocytes is activation of lyn kinase activity. We therefore sought to evaluate the activation of lyn kinase by LPS and Taxol in LPS-responsive (Lps(n)) and LPS-hyporesponsive (Lps(d)) macrophages. MATERIALS AND METHODS: C3H/OuJ (Lps(n)) and C3H/HeJ (Lps(d)) macrophages were stimulated by LPS or Taxol. Cell lysates were subjected to immunoprecipitation with anti-lyn antibody, gel electrophoresis, and in vitro kinase assays. Autoradiography and Phosphor-Imager analysis were carried out to detect incorporation of 32P into lyn protein. RESULTS: Within seconds of stimulation, LPS and Taxol induce in Lps(n) macrophages a depression of autophosphorylation, followed within minutes by autophosphorylation of both p53 and p56 lyn species. Lps(d) macrophages respond to LPS and Taxol with the initial decrease in activity, but fail to respond to LPS with autophosphorylation, and respond only to a limited extent upon Taxol stimulation. Tyrosine phosphatase inhibitors exerted inhibitory effects on LPS stimulation of lyn autophosphorylation. CONCLUSIONS: Decreased lyn kinase activity within seconds and autophosphorylation within minutes of LPS or Taxol stimulation in Lps(n) macrophages strongly supports the hypothesis that LPS and Taxol share a common signaling pathway. The finding that C3H/HeJ macrophages respond to LPS and Taxol with a normal depression of lyn activity, but fail to autophosphorylate lyn normally in response to LPS or Taxol, suggests that the Lps(d) defect is distal to LPS-receptor interaction. Finally, the inhibitory effect of tyrosine phosphatase inhibitors on LPS-induced lyn autophosphorylation suggests that tyrosine phosphatase(s) may participate in the regulation of lyn kinase activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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