Abstract
AbstractSignal transduction pathways constructed around a core module of three consecutive protein kinases, the most distal being a member of the extracellular signal‐regulated kinase (ERK) family, are ubiquitous among eukaryotes. Recent work has defined two cascades activated preferentially by the inflammatory cytokines TNF‐α and IL‐1‐β, as well as by a wide variety of cellular stresses such as UV and ionizing radiation, hyperosmolarity, heat stress, oxidative stress, etc. One pathway converges on the ERK subfamily known as the ‘stress activated’ protein kinases (SAPKs, also termed Jun N‐terminal kinases, JNKs), whereas the second pathway recruits the p38 kinases. Upstream inputs are diverse, and include small GTPases (primarily Rac and Cdc42; secondarily Ras) acting through mammalian homologs of the yeast Ste20 kinase, other kinase subfamilies (e.g. GC kinase) and ceramide, a putative second messenger for certain TNF‐α actions. These two cascades signal cell cycle delay, cellular repair or apoptosis in most cells, as well as activation of immune and reticuloendothelial cells.
References
70
Referenced
581
10.1038/369156a0
10.1016/0092-8674(94)90380-8
10.1126/science.7914033
10.1016/0092-8674(94)90277-1
10.1016/0092-8674(94)90278-X
10.1038/372739a0
10.1126/science.2164259
10.1016/0092-8674(91)90098-J
10.1016/0955-0674(95)80028-X
10.1016/0092-8674(95)90402-6
{'key': 'e_1_2_1_12_2', 'first-page': '17355', 'article-title': 'pp54 Microtubule‐associated protein 2 kinase', 'volume': '265', 'author': 'Kyriakis J. M.', 'year': '1990', 'journal-title': 'J. Biol. Chem.'}
/ J. Biol. Chem. / pp54 Microtubule‐associated protein 2 kinase by Kyriakis J. M. (1990)10.1016/S0021-9258(19)50735-9
/ J. Biol. Chem. / An array of insulin‐activated, prolinedirected (Ser/Thr) protein kinases phosphorylate the p70 S6 kinase by Mukhopadhyay N. K. (1992)10.1016/S0021-9258(18)99183-0
/ J. Biol. Chem. / pp54 Microtubule‐associated protein‐2 kinase requires both tyrosine and serine/threonine phosphorylation for activity by Kyriakis J. M. (1991)10.1016/0014-5793(92)80612-K
10.1016/0968-0004(94)90005-1
10.1128/MCB.14.12.8202
10.1074/jbc.270.21.12665
10.1038/343651a0
10.1016/0955-0674(92)90131-U
10.1074/jbc.270.13.7420
10.1016/0014-5793(92)81216-9
10.1002/j.1460-2075.1992.tb05492.x
10.1073/pnas.92.23.10531
10.1126/science.7839144
10.1038/369242a0
10.1126/science.7624781
10.1016/S0962-8924(00)89114-X
10.1038/353670a0
10.1128/MCB.14.12.8376
10.1016/0896-6273(95)90241-4
10.1126/science.7992057
10.1016/S0021-9258(18)47229-8
/ J. Biol. Chem. / The stress‐activated protein kinases are major c‐Jun amino‐terminal kinases activated by ischemia and reperfusion by Pombo C. M. (1994)10.1073/pnas.89.12.5341
10.1101/gad.7.11.2135
{'key': 'e_1_2_1_36_2', 'first-page': '849', 'article-title': 'Stress‐activated protein kinases bind directly to the d domain of c‐Jun in resting cells: implications for repression of c‐Jun function', 'volume': '10', 'author': 'Dai T.', 'year': '1995', 'journal-title': 'Oncogene'}
/ Oncogene / Stress‐activated protein kinases bind directly to the d domain of c‐Jun in resting cells: implications for repression of c‐Jun function by Dai T. (1995)10.1038/370226a0
10.1126/science.7824938
10.1210/me.6.12.2079
10.1074/jbc.270.50.30084
10.1126/science.7618106
10.1016/S0960-9822(95)00235-1
10.1038/372794a0
10.1038/372798a0
10.1016/S0962-8924(00)89055-8
-
Moriguchi T. Kawasaki H. Matsuda S. Gotoh Y.andNishida E.(1995).Evidence for multiple activators for stress‐activated protein kinases/c‐Jun amino‐terminal kinases.270 12969–12972.
(
10.1074/jbc.270.22.12969
) 10.1126/science.8385802
{'key': 'e_1_2_1_48_2', 'first-page': '1137', 'volume': '81', 'author': 'Coso O. A.', 'year': '1995', 'journal-title': 'The small GTP binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signalling pathway'}
/ The small GTP binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signalling pathway by Coso O. A. (1995)-
Minden A. Lin A. Claret F‐X. Abo A.andKarin M.(1995).Selective activation of the JNK signalling cascade and c‐Jun transcriptional activity by the small GTPases Rac and Cdc42Hs.81 1147–1157.
(
10.1016/S0092-8674(05)80019-4
) 10.1074/jbc.270.20.11757
10.1074/jbc.270.5.1979
/ J. Biol. Chem. / Protein kinase Byr2 is a target of Ras 1 in the fission yeast schizosaccharomyces pombe by Masuda T. (1995)10.1126/science.8073291
/ Science / Ras‐dependent growth factor regulation of MEK kinase in PC 12 cells by Lange‐Carter C. A. (1994)10.1126/science.7652575
10.1074/jbc.270.41.23934
10.1002/j.1460-2075.1992.tb05587.x
10.1038/367040a0
10.1038/376702a0
10.1002/j.1460-2075.1995.tb07189.x
/ EMBO J. / A novel serine kinase activated by rac1/CDC42Hs‐dependent autophosphorylation is related to PAK65 and STE20 by Martin G. A. (1995)10.1074/jbc.270.39.22731
/ J. Biol. Chem. / Identification of a mouse p21Cdc42/Rac activated kinase by Bragrodia S. (1995)10.1126/science.7618083
10.1101/gad.9.15.1817
10.1101/gad.8.18.2162
10.1016/S0021-9258(19)89463-2
/ J. Biol. Chem. / Differential expression of a novel protein kinase in human B lymphocytes by Katz P. (1994)10.1074/jbc.270.37.21695
10.1038/377750a0
10.1074/jbc.270.27.15984
10.1126/science.7667635
10.1074/jbc.270.39.22689
10.1016/S0021-9258(20)80686-3
/ J. Biol. Chem. / Substrate recognition by ceramide–activated protein kinase. Evidence that kinase activity is proline‐directed by Joseph C. K. (1993)10.1016/S0021-9258(17)41834-5
/ J. Biol. Chem. / The spingomyelin cycle and the second messenger function of ceramide by Hannun Y. (1994)10.1126/science.270.5240.1326
Dates
Type | When |
---|---|
Created | 20 years, 6 months ago (Feb. 25, 2005, 3:29 a.m.) |
Deposited | 1 year, 10 months ago (Oct. 26, 2023, 4:37 p.m.) |
Indexed | 3 weeks, 1 day ago (Aug. 7, 2025, 4:54 a.m.) |
Issued | 29 years, 1 month ago (July 1, 1996) |
Published | 29 years, 1 month ago (July 1, 1996) |
Published Online | 20 years, 6 months ago (Feb. 5, 2005) |
Published Print | 29 years, 1 month ago (July 1, 1996) |
@article{Kyriakis_1996, title={Protein kinase cascades activated by stress and inflammatory cytokines}, volume={18}, ISSN={1521-1878}, url={http://dx.doi.org/10.1002/bies.950180708}, DOI={10.1002/bies.950180708}, number={7}, journal={BioEssays}, publisher={Wiley}, author={Kyriakis, John M. and Avruch, Joseph}, year={1996}, month=jul, pages={567–577} }