Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages.
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Bacterial lipopolysaccharide (LPS) is a potent activator of antibacterial responses by macrophages. Following LPS stimulation, the tyrosine phosphorylation of several proteins is rapidly increased in macrophages, and this event appears to mediate some responses to LPS. We now report that two of these tyrosine phosphoproteins of 41 and 44 kDa are isoforms of mitogen-activated protein (MAP) kinase. Each of these proteins was reactive with anti-MAP kinase antibodies and comigrated with MAP kinase activity in fractions eluted from a MonoQ anion-exchange column. Following LPS stimulation, column fractions containing the tyrosine phosphorylated forms of p41 and p44 exhibited increased MAP kinase activity. Inhibition of LPS-induced tyrosine phosphorylation of these proteins was accompanied by inhibition of MAP kinase activity. Additionally, induction of p41/p44 tyrosine phosphorylation and MAP kinase activity by LPS appeared to be independent of activation of protein kinase C, even though phorbol esters also induced these responses. These results demonstrate that LPS induces the tyrosine phosphorylation and activation of at least two MAP kinase isozymes. Since MAP kinases appear to modulate cellular processes in response to extracellular signals, these kinases may be important targets for LPS action in macrophages.
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LPS activates three subclasses of MAPKs in macrophages and other cells: ERK, JNK, and p38; some compounds suppress proinflammatory cytokines and NF-κB and inhibit COX-2 and iNOS expression by inhibiting some of these MAPKs.
“In macrophages and other types of cells, LPS activates three subclasses of MAPKs: extracellular signal-regulated kinase (ERK), c-Jun-terminal kinase (JNK) and p38. Studies have revealed that some compounds are able to suppress proinflammatory cytokines and NF-κB, to inhibit the COX-2 and iNOS expression inhibiting some of these MAPKS [129,130,131].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [130]
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- Authors
- Weinstein, S. L., Sanghera, J. S., Lemke, K., DeFranco, A. L., & Pelech, S. L.
- Affiliations
- University of California, San Francisco (US)
- Genentech (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1992-07
- Volume
- 267
- Issue
- 21
- Pages
- 14955-14962
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1671728707
- Cited by
- 396
- References
- 31
- Citations by year
- 2026: 2 · 2024: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 4 · 2012: 8
- FWCI
- 8.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI20038)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- lipopolysaccharide, macrophages, tyrosine phosphorylation, mitogen-activated protein kinase, signal transduction, phorbol ester, antibacterial response
- MeSH terms
- Amino Acid Sequence, Animals, Cells, Cultured, Chromatography, Ion Exchange, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Isoenzymes, Lipopolysaccharides, Macrophages, Molecular Sequence Data, Peptides, Phosphorylation, Precipitin Tests, Protein Kinase C, Protein Kinases, Quinones, Tyrosine, Blotting, Western, Benzoquinones, Rifabutin, Calcium-Calmodulin-Dependent Protein Kinases, Lactams, Macrocyclic, Protein Kinase Inhibitors, Mice
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