Protein-tyrosine phosphatase inhibitors block tumor necrosis factor-dependent activation of the nuclear transcription factor NF-kappa B
- PMID: 7738000
- DOI: 10.1074/jbc.270.18.10631
Protein-tyrosine phosphatase inhibitors block tumor necrosis factor-dependent activation of the nuclear transcription factor NF-kappa B
Abstract
Most of the inflammatory and proviral effects of tumor necrosis factor (TNF) are mediated through the activation of the nuclear transcription factor NF-kappa B. How TNF activates NF-kappa B, however, is not well understood. We examined the role of protein phosphatases in the TNF-dependent activation of NF-kappa B. Treatment of human myeloid ML-1a cells with TNF rapidly activated (within 30 min) NF-kappa B; this effect was abolished by treating cells with inhibitors of protein-tyrosine phosphatase (PTPase), including phenylarsine oxide (PAO), pervanadate, and diamide. The inhibition was dependent on the dose and occurred whether added before or at the same time as TNF. PAO also inhibited the activation even when added 15 min after the TNF treatment of cells. In contrast to inhibitors of PTPase, okadaic acid and calyculin A, which block serine-threonine phosphatase, had no effect. The effect of PTPase inhibitors was not due to the modulation of TNF receptors. Since both dithiothreitol and dimercaptopropanol reversed the inhibitory effect of PAO, critical sulfhydryl groups in the PTPase must be involved in NF-kappa B activation by TNF. PTPase inhibitors also blocked NF-kappa B activation induced by phorbol ester, ceramide, and interleukin-1 but not that activated by okadaic acid. The degradation of I kappa B protein, a critical step in NF-kappa B activation, was also abolished by the PTPase inhibitors as revealed by immunoblotting. Thus, overall, we demonstrate that PTPase is involved either directly or indirectly in the pathway leading to the activation of NF-kappa B.
Similar articles
-
Induction of endothelial cell surface adhesion molecules by tumor necrosis factor is blocked by protein tyrosine phosphatase inhibitors: role of the nuclear transcription factor NF-kappa B.Eur J Immunol. 1997 Sep;27(9):2172-9. doi: 10.1002/eji.1830270909. Eur J Immunol. 1997. PMID: 9341756
-
Involvement of a putative protein-tyrosine phosphatase and I kappa B-alpha serine phosphorylation in nuclear factor kappa B activation by tumor necrosis factor.J Biol Chem. 1995 Aug 11;270(32):18881-7. doi: 10.1074/jbc.270.32.18881. J Biol Chem. 1995. PMID: 7642544
-
Activation of NF-kappa B by phosphatase inhibitors involves the phosphorylation of I kappa B alpha at phosphatase 2A-sensitive sites.J Biol Chem. 1995 Aug 4;270(31):18347-51. doi: 10.1074/jbc.270.31.18347. J Biol Chem. 1995. PMID: 7629157
-
Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression.J Immunol. 1999 Feb 15;162(4):2095-102. J Immunol. 1999. PMID: 9973483
-
Protein tyrosine kinase inhibitors block tumor necrosis factor-induced activation of nuclear factor-kappaB, degradation of IkappaBalpha, nuclear translocation of p65, and subsequent gene expression.Arch Biochem Biophys. 1998 Apr 1;352(1):59-70. doi: 10.1006/abbi.1998.0576. Arch Biochem Biophys. 1998. PMID: 9521814
Cited by
-
Selective involvement of reactive oxygen intermediates in platelet-activating factor-mediated activation of NF-kappaB.Inflammation. 2000 Oct;24(5):385-98. doi: 10.1023/a:1007068010645. Inflammation. 2000. PMID: 10921504
-
Advances in Immunosuppressive Agents Based on Signal Pathway.Front Pharmacol. 2022 May 26;13:917162. doi: 10.3389/fphar.2022.917162. eCollection 2022. Front Pharmacol. 2022. PMID: 35694243 Free PMC article. Review.
-
The novel function of advanced glycation end products in regulation of MMP-9 production.J Surg Res. 2011 Dec;171(2):871-6. doi: 10.1016/j.jss.2010.04.027. Epub 2010 May 11. J Surg Res. 2011. PMID: 20638679 Free PMC article.
-
WIP1 phosphatase is a negative regulator of NF-kappaB signalling.Nat Cell Biol. 2009 May;11(5):659-66. doi: 10.1038/ncb1873. Epub 2009 Apr 19. Nat Cell Biol. 2009. PMID: 19377466
-
beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha.Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8603-7. doi: 10.1073/pnas.0402851101. Epub 2004 Jun 1. Proc Natl Acad Sci U S A. 2004. PMID: 15173580 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
