A protein kinase involved in the regulation of inflammatory cytokine biosynthesis.

doi:10.1038/372739A0

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A protein kinase involved in the regulation of inflammatory cytokine biosynthesis.

Journal Article•DOI•

A protein kinase involved in the regulation of inflammatory cytokine biosynthesis.

Joseph C. Lee, Jeffrey T. Laydon, Peter C. McDonnell, Timothy Gallagher, Sanjay Kumar, David W. Green¹, Dean E. McNulty, M. J. Blumenthal, J. R. Heys, S. W. Landvatter, James E. Strickler, Megan M. McLaughlin, I. R. Siemens, Seth M. Fisher, George P. Livi, John R. White, Jerry L. Adams, Peter Young - Show less +14 more•Institutions (1)

Bristol-Myers Squibb¹

01 Dec 1994-Nature (Nature Publishing Group)-Vol. 372, Iss: 6508, pp 739-746

TL;DR: Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds, suggesting that the CSBPs are critical for cytokine production.

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Abstract: Production of interleukin-1 and tumour necrosis factor from stimulated human monocytes is inhibited by a new series of pyridinyl-imidazole compounds. Using radiolabelled and radio-photoaffinity-labelled chemical probes, the target of these compounds was identified as a pair of closely related mitogen-activated protein kinase homologues, termed CSBPs. Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production.

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Journal Article•DOI•

Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis

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Zhengui Xia¹, Martin Dickens², Joel Raingeaud², Roger J. Davis², Michael E. Greenberg¹ - Show less +1 more•Institutions (2)

Harvard University¹, University of Massachusetts Medical School²

24 Nov 1995-Science

TL;DR: The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells.

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Abstract: Apoptosis plays an important role during neuronal development, and defects in apoptosis may underlie various neurodegenerative disorders. To characterize molecular mechanisms that regulate neuronal apoptosis, the contributions to cell death of mitogen-activated protein (MAP) kinase family members, including ERK (extracellular signal-regulated kinase), JNK (c-JUN NH2-terminal protein kinase), and p38, were examined after withdrawal of nerve growth factor (NGF) from rat PC-12 pheochromocytoma cells. NGF withdrawal led to sustained activation of the JNK and p38 enzymes and inhibition of ERKs. The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells. Therefore, the dynamic balance between growth factor-activated ERK and stress-activated JNK-p38 pathways may be important in determining whether a cell survives or undergoes apoptosis.

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5,398 citations

Journal Article•DOI•

Biologic basis for interleukin-1 in disease

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Charles A. Dinarello¹•Institutions (1)

Tufts University¹

15 Mar 1996-Blood

TL;DR: This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references, which summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.

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4,354 citations

Journal Article•DOI•

Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.

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Gray W. Pearson, Fred L. Robinson¹, Tara Beers Gibson¹, Bing E. Xu¹, Mahesh Karandikar¹, Kevin S. Berman¹, Melanie H. Cobb - Show less +3 more•Institutions (1)

University of Texas Southwestern Medical Center¹

01 Apr 2001-Endocrine Reviews

TL;DR: Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted and particular emphasis is on ERK1/2.

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Abstract: Mitogen-activated protein (MAP) kinases comprise a family of ubiquitous proline-directed, protein-serine/threonine kinases, which participate in signal transduction pathways that control intracellular events including acute responses to hormones and major developmental changes in organisms. MAP kinases lie in protein kinase cascades. This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2.

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4,040 citations

Cites background from "A protein kinase involved in the re..."

...Mammalian MAP Kinases MAP Kinase Other names Comments P Site motif References ERK1 p44 MAPK .80% identical to ERK2; abundant and ubiquitous TEY (5) ERK2 p42 MAPK Abundant and ubiquitous TEY (7) ERK3a p63, rat ERK3 Immunoblotting detects 63K and full-length 95–100K species; a is present in many species including human SEG (7) ERK3b Human ERK3 ;75% identical to ERK3a SEG (59) ERK1b (ERK4) 46K splice form of ERK1; comigrates with band originally named ERK4 TEY (60) JNK1 SAPKg Multiple spliced forms TPY (14, 15, 121) JNK2 SAPKa Multiple spliced forms TPY (14, 15, 121) JNK3 SAPKb Multiple spliced forms TPY (14, 15, 121) p38a p38, CSBP, SAPK2 Sensitive to SB203580 TGY (16–18) p38b p38-2 Partially sensitive to SB203580 TGY (138, 137) p38b2 Sensitive to SB203580; lacks the 8-amino acid insertion unique to p38b TGY (142) p38g ERK6, SAPK3 Insensitive to SB203580 TGY (140, 143) p38d SAPK4 Insensitive to SB203580 TGY (139, 141, 142) Mxi p38a splice form lacking 80 C-t residues and containing 17 novel ones TGY (146) ERK5 Involved in proliferation TEY (160, 161) ERK7 May have a role in cell proliferation TEY (175) NLK Nemo-like kinase Regulation of Wnt pathway; ortholog of C. elegans LIT-1; relative of Drosophila nemo TQEa (24) MAK Male germ cell associated kinase Expressed in cells undergoing meiosis in the testis but not ovary TDY (179) MRK MAK-related kinase Expressed in embryonic myocardium; ubiquitous in adult tissues TDY (180) MOK Phorbol ester sensitive TEY (178) KKIALRE Cdc2-related kinase TDY (22) KKIAMRE T, Y mutants still activated in cells TDY (23) a The CDK phosphorylation site motif is THE and the sequence of the nematode homolog of NLK is THE. eral MEK family members contain sites that are phosphorylated by kinases in other pathways; these events may influence the ability of MEKs to interact in complexes, for instance (32, 53, 54)....
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...As noted above, p38 was identified as the target of compound discovered in a cell-based screen for inhibitors of lipopolysaccharide (LPS)-induced TNFa and IL-1b production in monocytes (16)....
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...It was found as a tyrosine phosphoprotein present in extracts of cells treated with inflammatory cytokines (17); as the target of a pyridinyl imidazole drug that blocked production of tumor necrosis factor-a (TNFa) and as such was called cytokine-suppressive antiinflammatory drug-binding protein or CSBP (16); and as a reactivating kinase for MAP kinaseactivated protein (MAPKAP) kinase-2 (18)....
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Journal Article•DOI•

Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases

[...]

Gary L. Johnson¹, Razvan Lapadat¹•Institutions (1)

Anschutz Medical Campus¹

06 Dec 2002-Science

TL;DR: Multicellular organisms have three well-characterized subfamilies of mitogen-activated protein kinases (MAPKs) that control a vast array of physiological processes, and inhibitors of these enzymes are being explored as anticancer agents.

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Abstract: Multicellular organisms have three well-characterized subfamilies of mitogen-activated protein kinases (MAPKs) that control a vast array of physiological processes. These enzymes are regulated by a characteristic phosphorelay system in which a series of three protein kinases phosphorylate and activate one another. The extracellular signal-regulated kinases (ERKs) function in the control of cell division, and inhibitors of these enzymes are being explored as anticancer agents. The c-Jun amino-terminal kinases (JNKs) are critical regulators of transcription, and JNK inhibitors may be effective in control of rheumatoid arthritis. The p38 MAPKs are activated by inflammatory cytokines and environmental stresses and may contribute to diseases like asthma and autoimmunity.

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3,999 citations

Journal Article•DOI•

PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in Vivo

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Dario R. Alessi¹, Ana Cuenda¹, Philip Cohen¹, David T. Dudley², Alan R. Saltiel² - Show less +1 more•Institutions (2)

University of Dundee¹, Parke-Davis²

17 Nov 1995-Journal of Biological Chemistry

TL;DR: The results indicate that the activation of Raf is suppressed and that its inactivation is accelerated by a downstream component(s) of the MAP kinase pathway.

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3,444 citations

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Journal Article•DOI•

Basic Local Alignment Search Tool

[...]

Stephen F. Altschul¹, Warren Gish¹, Webb Miller², Eugene W. Myers³, David J. Lipman¹ - Show less +1 more•Institutions (3)

National Institutes of Health¹, Pennsylvania State University², University of Arizona³

01 Oct 1990-Journal of Molecular Biology

TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.

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88,255 citations

Journal Article•DOI•

The protein kinase family: conserved features and deduced phylogeny of the catalytic domains.

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Steven K. Hanks¹, Anne Marie Quinn, Tony Hunter•Institutions (1)

Salk Institute for Biological Studies¹

01 Jul 1988-Science

TL;DR: Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.

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Abstract: In recent years, members of the protein kinase family have been discovered at an accelerated pace. Most were first described, not through the traditional biochemical approach of protein purification and enzyme assay, but as putative protein kinase amino acid sequences deduced from the nucleotide sequences of molecularly cloned genes or complementary DNAs. Phylogenetic mapping of the conserved protein kinase catalytic domains can serve as a useful first step in the functional characterization of these newly identified family members.

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4,838 citations

Journal Article•DOI•

JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain

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Benoit Dérijard¹, Benoit Dérijard², Masahiko Hibi¹, I-Huan Wu², I-Huan Wu¹, Tamera Barrett¹, Bing Su¹, Tiliang Deng¹, Michael Karin¹, Roger J. Davis², Roger J. Davis¹ - Show less +7 more•Institutions (2)

University of Massachusetts Medical School¹, University of California, San Diego²

25 Mar 1994-Cell

TL;DR: JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation and its properties indicate that JNK1 activation may play an important role in tumor promotion.

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3,232 citations

Journal Article•DOI•

A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells

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Jiahuai Han¹, JD Lee, L Bibbs, Richard J. Ulevitch•Institutions (1)

Scripps Research Institute¹

05 Aug 1994-Science

TL;DR: Findings link a signaling pathway in mammalian cells with a pathway in yeast that is responsive to physiological stress.

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Abstract: Mammalian cells respond to endotoxic lipopolysaccharide (LPS) by activation of protein kinase cascades that lead to new gene expression. A protein kinase, p38, that was tyrosine phosphorylated in response to LPS, was cloned. The p38 enzyme and the product of the Saccharomyces cerevisiae HOG1 gene, which are both members of the mitogen-activated protein (MAP) kinase family, have sequences at and adjacent to critical phosphorylation sites that distinguish these proteins from most other MAP kinase family members. Both HOG1 and p38 are tyrosine phosphorylated after extracellular changes in osmolarity. These findings link a signaling pathway in mammalian cells with a pathway in yeast that is responsive to physiological stress.

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2,673 citations

Journal Article•DOI•

The stress-activated protein kinase subfamily of c-Jun kinases.

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John M. Kyriakis¹, Papia Banerjee¹, Eleni Nikolakaki², Eleni Nikolakaki¹, Tianang Dai¹, Elizabeth A. Rubie¹, M. F. Ahmad¹, Joseph Avruch¹, James R. Woodgett¹ - Show less +5 more•Institutions (2)

Harvard University¹, Aristotle University of Thessaloniki²

12 May 1994-Nature

TL;DR: The kinase p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-α, hence they are designated stress-activated protein kinases, or SAPKs.

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Abstract: The mitogen-activated protein (MAP) kinases Erk-1 and Erk-2 are proline-directed kinases that are themselves activated through concomitant phosphorylation of tyrosine and threonine residues. The kinase p54 (M(r) 54,000), which was first isolated from cycloheximide-treated rats, is proline-directed like Erks-1/2, and requires both Tyr and Ser/Thr phosphorylation for activity. p54 is, however, distinct from Erks-1/2 in its substrate specificity, being unable to phosphorylate pp90rsk but more active in phosphorylating the c-Jun transactivation domain. Molecular cloning of p54 reveals a unique subfamily of extracellularly regulated kinases. Although they are 40-45% identical in sequence to Erks-1/2, unlike Erks-1/2 the p54s are only poorly activated in most cells by mitogens or phorbol esters. However, p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-alpha, hence they are designated stress-activated protein kinases, or SAPKs. SAPKs are also activated by sphingomyelinase, which elicits a subset of cellular responses to TNF-alpha (ref. 9). SAPKs therefore define a new TNF-alpha and stress-activated signalling pathway, possibly initiated by sphingomyelin-based second messengers, which regulates the activity of c-Jun.

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2,628 citations