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Physiol. Rev. 81: 807-869, 2001;
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Physiological Reviews, Vol. 81, No. 2, April 2001, pp. 807-869
Copyright ©2001 by the American Physiological Society

Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation

John M. Kyriakis and Joseph Avruch

Diabetes Research Laboratory, Medical Services, and Department of Molecular Biology, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts

Kyriakis, John M. and Joseph Avruch. Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation. Physiol. Rev. 81: 807-869, 2001.The molecular details of mammalian stress-activated signal transduction pathways have only begun to be dissected. This, despite the fact that the impact of these pathways on the pathology of chronic inflammation, heart disease, stroke, the debilitating effects of diabetes mellitus, and the side effects of cancer therapy, not to mention embryonic development, innate and acquired immunity, is profound. Cardiovascular disease and diabetes alone represent the most significant health care problems in the developed world. Thus it is not surprising that understanding these pathways has attracted wide interest, and in the past 10 years, dramatic progress has been made. Accordingly, it is now becoming possible to envisage the transition of these findings to the development of novel treatment strategies. This review focuses on the biochemical components and regulation of mammalian stress-regulated mitogen-activated protein kinase (MAPK) pathways. The nuclear factor-kappa B pathway, a second stress signaling paradigm, has been the subject of several excellent recent reviews (258, 260).




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P. S. Wolf, H. E. Merry, A. S. Farivar, A. S. McCourtie, and M. S. Mulligan
Stress-activated protein kinase inhibition to ameliorate lung ischemia reperfusion injury
J. Thorac. Cardiovasc. Surg., March 1, 2008; 135(3): 656 - 665.
[Abstract] [Full Text] [PDF]

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 JDRHome page
M. Handfield, H.V. Baker, and R.J. Lamont
Beyond Good and Evil in the Oral Cavity: Insights into Host-Microbe Relationships Derived from Transcriptional Profiling of Gingival Cells
Journal of Dental Research, March 1, 2008; 87(3): 203 - 223.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
T. Nagashima, T. Maruyama, H. Uchida, T. Kajitani, T. Arase, M. Ono, H. Oda, M. Kagami, H. Masuda, S. Nishikawa, et al.
Activation of SRC Kinase and Phosphorylation of Signal Transducer and Activator of Transcription-5 Are Required for Decidual Transformation of Human Endometrial Stromal Cells
Endocrinology, March 1, 2008; 149(3): 1227 - 1234.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
T. Kawasaki, M. A. Choudhry, M. G. Schwacha, S. Fujimi, J. A. Lederer, K. I. Bland, and I. H. Chaudry
Trauma-hemorrhage inhibits splenic dendritic cell proinflammatory cytokine production via a mitogen-activated protein kinase process
Am J Physiol Cell Physiol, March 1, 2008; 294(3): C754 - C764.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
E. Laaksamo, R. Tulamo, M. Baumann, R. Dashti, J. Hernesniemi, S. Juvela, M. Niemela, and A. Laakso
Involvement of Mitogen-Activated Protein Kinase Signaling in Growth and Rupture of Human Intracranial Aneurysms
Stroke, March 1, 2008; 39(3): 886 - 892.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
V. Tchaikovski, G. Fellbrich, and J. Waltenberger
The Molecular Basis of VEGFR-1 Signal Transduction Pathways in Primary Human Monocytes
Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 322 - 328.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Abrahams, S. Mowla, M. I. Parker, C. R. Goding, and S. Prince
UV-mediated Regulation of the Anti-senescence Factor Tbx2
J. Biol. Chem., January 25, 2008; 283(4): 2223 - 2230.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
X. Chen, M. Rzhetskaya, T. Kareva, R. Bland, M. J. During, A. W. Tank, N. Kholodilov, and R. E. Burke
Antiapoptotic and Trophic Effects of Dominant-Negative Forms of Dual Leucine Zipper Kinase in Dopamine Neurons of the Substantia Nigra In Vivo
J. Neurosci., January 16, 2008; 28(3): 672 - 680.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
N. Eckstein, K. Servan, L. Girard, D. Cai, G. von Jonquieres, U. Jaehde, M. U. Kassack, A. F. Gazdar, J. D. Minna, and H.-D. Royer
Epidermal Growth Factor Receptor Pathway Analysis Identifies Amphiregulin as a Key Factor for Cisplatin Resistance of Human Breast Cancer Cells
J. Biol. Chem., January 11, 2008; 283(2): 739 - 750.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
M. Cabanski, M. Steinmuller, L. M. Marsh, E. Surdziel, W. Seeger, and J. Lohmeyer
PKR Regulates TLR2/TLR4-Dependent Signaling in Murine Alveolar Macrophages
Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 26 - 31.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. Garcia-Herrera, M. C. Marca, E. Brot-Laroche, N. Guillen, S. Acin, M. A. Navarro, J. Osada, and M. J. Rodriguez-Yoldi
Protein kinases, TNF-{alpha}, and proteasome contribute in the inhibition of fructose intestinal transport by sepsis in vivo
Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G155 - G164.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
H. Morimoto, K. Kondoh, S. Nishimoto, K. Terasawa, and E. Nishida
Activation of a C-terminal Transcriptional Activation Domain of ERK5 by Autophosphorylation
J. Biol. Chem., December 7, 2007; 282(49): 35449 - 35456.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Nunez, M. L. Laorden, and M. V. Milanes
Regulation of Serine (Ser)-31 and Ser40 Tyrosine Hydroxylase Phosphorylation during Morphine Withdrawal in the Hypothalamic Paraventricular Nucleus and Nucleus Tractus Solitarius-A2 Cell Group: Role of ERK1/2
Endocrinology, December 1, 2007; 148(12): 5780 - 5793.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. J. O'Keefe, J. S. Mudgett, S. Cupo, J. N. Parsons, N. A. Chartrain, C. Fitzgerald, S.-L. Chen, K. Lowitz, C. Rasa, D. Visco, et al.
Chemical Genetics Define the Roles of p38{alpha} and p38 in Acute and Chronic Inflammation
J. Biol. Chem., November 30, 2007; 282(48): 34663 - 34671.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
N. J. Kang, K. W. Lee, E. A. Rogozin, Y.-Y. Cho, Y.-S. Heo, A. M. Bode, H. J. Lee, and Z. Dong
Equol, a Metabolite of the Soybean Isoflavone Daidzein, Inhibits Neoplastic Cell Transformation by Targeting the MEK/ERK/p90RSK/Activator Protein-1 Pathway
J. Biol. Chem., November 9, 2007; 282(45): 32856 - 32866.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
F. Y. Ma, G. H. Tesch, R. A. Flavell, R. J. Davis, and D. J. Nikolic-Paterson
MKK3-p38 signaling promotes apoptosis and the early inflammatory response in the obstructed mouse kidney
Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1556 - F1563.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
G.-X. Zhang, X.-M. Lu, S. Kimura, and A. Nishiyama
Role of mitochondria in angiotensin II-induced reactive oxygen species and mitogen-activated protein kinase activation
Cardiovasc Res, November 1, 2007; 76(2): 204 - 212.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. Mishra, M. K. Barthwal, G. Sondarva, B. Rana, L. Wong, M. Chatterjee, J. R. Woodgett, and A. Rana
Glycogen Synthase Kinase-3beta Induces Neuronal Cell Death via Direct Phosphorylation of Mixed Lineage Kinase 3
J. Biol. Chem., October 19, 2007; 282(42): 30393 - 30405.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
G.-X. Zhang, Y. Nagai, T. Nakagawa, H. Miyanaka, Y. Fujisawa, A. Nishiyama, K. Izuishi, K. Ohmori, and S. Kimura
Involvement of endogenous nitric oxide in angiotensin II-induced activation of vascular mitogen-activated protein kinases
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2403 - H2408.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
P. J. Nadeau, S. J. Charette, M. B. Toledano, and J. Landry
Disulfide Bond-mediated Multimerization of Ask1 and Its Reduction by Thioredoxin-1 Regulate H2O2-induced c-Jun NH2-terminal Kinase Activation and Apoptosis
Mol. Biol. Cell, October 1, 2007; 18(10): 3903 - 3913.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
C.-H. Teng, W.-N. Huang, and T.-C. Meng
Several Dual Specificity Phosphatases Coordinate to Control the Magnitude and Duration of JNK Activation in Signaling Response to Oxidative Stress
J. Biol. Chem., September 28, 2007; 282(39): 28395 - 28407.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
Y. Wang
Mitogen-Activated Protein Kinases in Heart Development and Diseases
Circulation, September 18, 2007; 116(12): 1413 - 1423.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. Chen, S. Reierstad, Z. Lin, M. Lu, C. Brooks, N. Li, J. Innes, and S. E. Bulun
Prostaglandin E2 Induces Breast Cancer Related Aromatase Promoters via Activation of p38 and c-Jun NH2-Terminal Kinase in Adipose Fibroblasts
Cancer Res., September 15, 2007; 67(18): 8914 - 8922.
[Abstract] [Full Text] [PDF]

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 JEMHome page
Y. Kim, P. Zhou, L. Qian, J.-Z. Chuang, J. Lee, C. Li, C. Iadecola, C. Nathan, and A. Ding
MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
J. Exp. Med., September 3, 2007; 204(9): 2063 - 2074.
[Abstract] [Full Text] [PDF]

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 JDRHome page
J.F. Schindler, J.B. Monahan, and W.G. Smith
p38 Pathway Kinases as Anti-inflammatory Drug Targets
Journal of Dental Research, September 1, 2007; 86(9): 800 - 811.
[Abstract] [Full Text] [PDF]

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 Reproductive SciencesHome page
Wenjing Zhong, Yufen Xie, Yingchun Wang, J. Lewis, A. Trostinskaia, Fangfei Wang, E. E. Puscheck, and D. A. Rappolee
Use of Hyperosmolar Stress to Measure Stress-Activated Protein Kinase Activation and Function in Human HTR Cells and Mouse Trophoblast Stem Cells
Reproductive Sciences, September 1, 2007; 14(6): 534 - 547.
[Abstract] [PDF]

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 CarcinogenesisHome page
G. D. Lu, H.-M. Shen, M. C.M. Chung, and C. N. Ong
Critical role of oxidative stress and sustained JNK activation in aloe-emodin-mediated apoptotic cell death in human hepatoma cells
Carcinogenesis, September 1, 2007; 28(9): 1937 - 1945.
[Abstract] [Full Text] [PDF]

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 Sci SignalHome page
H. Sumimoto, S. Kamakura, and T. Ito
Structure and Function of the PB1 Domain, a Protein Interaction Module Conserved in Animals, Fungi, Amoebas, and Plants
Sci. Signal., August 28, 2007; 2007(401): re6 - re6.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. S. Lee and B. E. Ellis
Arabidopsis MAPK Phosphatase 2 (MKP2) Positively Regulates Oxidative Stress Tolerance and Inactivates the MPK3 and MPK6 MAPKs
J. Biol. Chem., August 24, 2007; 282(34): 25020 - 25029.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
J. Zhong and J. M. Kyriakis
Dissection of a Signaling Pathway by Which Pathogen-associated Molecular Patterns Recruit the JNK and p38 MAPKs and Trigger Cytokine Release
J. Biol. Chem., August 17, 2007; 282(33): 24246 - 24254.
[Abstract] [Full Text] [PDF]

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 Innate ImmunityHome page
S.-i. Tanabe, C. Bodet, and D. Grenier
Peptostreptococcus micros cell wall elicits a pro-inflammatory response in human macrophages
Innate Immunity, August 1, 2007; 13(4): 219 - 226.
[Abstract] [PDF]

Home page
 Infect. Immun.Home page
G. K. A. Meyer, A. Neetz, G. Brandes, D. Tsikas, J. H. Butterfield, I. Just, and R. Gerhard
Clostridium difficile Toxins A and B Directly Stimulate Human Mast Cells
Infect. Immun., August 1, 2007; 75(8): 3868 - 3876.
[Abstract] [Full Text] [PDF]

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 Nephrol Dial TransplantHome page
M. S. Razzaque
Cisplatin nephropathy: is cytotoxicity avoidable?
Nephrol. Dial. Transplant., August 1, 2007; 22(8): 2112 - 2116.
[Full Text] [PDF]


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