{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T20:19:13Z","timestamp":1774988353709,"version":"3.50.1"},"reference-count":58,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[1997,2,1]],"date-time":"1997-02-01T00:00:00Z","timestamp":854755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Opinion in Genetics & Development"],"published-print":{"date-parts":[[1997,2]]},"DOI":"10.1016\/s0959-437x(97)80111-6","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T10:21:15Z","timestamp":1027592475000},"page":"67-74","source":"Crossref","is-referenced-by-count":256,"title":["MEKKs, GCKs, MLKs, PAKs, TAKs, and Tpls: upstream regulators of the c-Jun amino-terminal kinases?"],"prefix":"10.1016","volume":"7","author":[{"given":"Gary R","family":"Fanger","sequence":"first","affiliation":[]},{"given":"P\u00e4r","family":"Gerwins","sequence":"additional","affiliation":[]},{"given":"Christian","family":"Widmann","sequence":"additional","affiliation":[]},{"given":"Matthew B","family":"Jarpe","sequence":"additional","affiliation":[]},{"given":"Gary L","family":"Johnson","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/S0959-437X(97)80111-6_BIB1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/0955-0674(94)90141-4","article-title":"Sequential protein kinase reactions controlling cell growth and differentiation","volume":"6","author":"Johnson","year":"1994","journal-title":"Curr Opin Cell Biol"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1096\/fasebj.9.9.7601337","article-title":"The MAPK signaling cascade","volume":"9","author":"Seger","year":"1995","journal-title":"FASEB J"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB3","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/372739a0","article-title":"A protein kinase involved in the regulation of inflammatory cytokine biosynthesis","volume":"372","author":"Lee","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/380075a0","article-title":"Requirement for ceramide-initiated SAPK\/JNK signaling in stress-induced apoptosis","volume":"380","author":"Verheij","year":"1996","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB5_1","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1126\/science.270.5240.1326","article-title":"Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis","volume":"270","author":"Xia","year":"1995","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB6","doi-asserted-by":"crossref","first-page":"3229","DOI":"10.1074\/jbc.271.6.3229","article-title":"Signal transduction pathways regulated by mitogen-activated\/extracellular response kinase kinase kinase induce cell death","volume":"271","author":"Lassignal-Johnson","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB7","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0092-8674(00)81375-6","article-title":"Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-\u03baB activation prevents cell death","volume":"87","author":"Liu","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB8_1","doi-asserted-by":"crossref","first-page":"14560","DOI":"10.1074\/jbc.271.24.14560","article-title":"Fibroblast growth factor-2 suppression of tumor necrosis factor \u03b1-mediated apoptosis requires ras and the activation of mitogen-activated protein kinase","volume":"271","author":"Gardner","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB9_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0092-8674(95)90402-6","article-title":"MAP kinase pathways in yeast: for mating and more","volume":"80","author":"Herskowitz","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB10_1","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.7839144","article-title":"Independent human MAP kinase signal transduction pathways defined by MEK and MKK isoforms","volume":"267","author":"Derijard","year":"1995","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB11","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/372794a0","article-title":"Role of SAPK\/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun","volume":"372","author":"Sanchez","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB12","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/369156a0","article-title":"The stress-activated protein kinase subfamily of c-Jun kinases","volume":"369","author":"Kyriakis","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB13","doi-asserted-by":"crossref","first-page":"5361","DOI":"10.1074\/jbc.271.10.5361","article-title":"Molecular cloning of mitogen-activated protein\/ERK kinase kinases (MEKK) 2 and 3","volume":"271","author":"Blank","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB14","first-page":"641","article-title":"Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK","volume":"12","author":"Hirai","year":"1996","journal-title":"Oncogene"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB15","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/377750a0","article-title":"Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase","volume":"377","author":"Pombo","year":"1995","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB16","doi-asserted-by":"crossref","first-page":"19025","DOI":"10.1074\/jbc.271.32.19025","article-title":"The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1","volume":"271","author":"Rana","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB17_1","doi-asserted-by":"crossref","first-page":"27225","DOI":"10.1074\/jbc.271.44.27225","article-title":"Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase\/stress activated protein kinase pathway","volume":"271","author":"Teramoto","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB18","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/372798a0","article-title":"Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1","volume":"372","author":"Yan","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB19","doi-asserted-by":"crossref","first-page":"25070","DOI":"10.1074\/jbc.270.42.25070","article-title":"Molecular cloning of a new member of the p21-Cdc42\/Rac-activated kinase (PAK) family","volume":"270","author":"Manser","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/367040a0","article-title":"A brain serine\/threonine protein kinase activated by Cdc42 and Rac1","volume":"367","author":"Manser","year":"1994","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB21","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1002\/j.1460-2075.1995.tb07189.x","article-title":"A novel serine kinase activated by rac1\/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20","volume":"14","author":"Martin","year":"1995","journal-title":"EMBO J"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB22_1","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/S0092-8674(05)80018-2","article-title":"The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK\/SAPK signaling pathway","volume":"81","author":"Coso","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB23_1","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0092-8674(05)80019-4","article-title":"Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs","volume":"81","author":"Minden","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S0968-0004(96)10022-0","article-title":"Rho family GTPases: the cytoskeleton and beyond","volume":"21","author":"Symons","year":"1996","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB25","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0092-8674(95)90023-3","article-title":"Rho family members: activators of MAP kinase cascades","volume":"82","author":"Vojtek","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB26","doi-asserted-by":"crossref","first-page":"23934","DOI":"10.1074\/jbc.270.41.23934","article-title":"Rho family GTPases regulates p38 mitogen-activated protein kinase through the downstream mediator Pak1","volume":"270","author":"Zhang","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB27","doi-asserted-by":"crossref","first-page":"7420","DOI":"10.1074\/jbc.270.13.7420","article-title":"Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine","volume":"270","author":"Raingeaud","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB28","doi-asserted-by":"crossref","first-page":"4867","DOI":"10.4049\/jimmunol.156.12.4867","article-title":"Activation of a p38 mitogen-activated kinase in human neutrophils by lipopolysaccharide","volume":"156","author":"Nick","year":"1996","journal-title":"J Immunol"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB29","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1126\/science.272.5266.1347","article-title":"Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP kinase","volume":"272","author":"Wang","year":"1996","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB30","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/383547a0","article-title":"A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation","volume":"383","author":"Dikic","year":"1996","journal-title":"Nature"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB31","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1126\/science.273.5276.792","article-title":"Activation of Pyk2 by stress signals and coupling with JNK signaling pathway","volume":"273","author":"Tokiwa","year":"1996","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0092-8674(95)90406-9","article-title":"Modular binding domains in signal transduction proteins","volume":"80","author":"Cohen","year":"1995","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB33","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1126\/science.8385802","article-title":"A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf","volume":"260","author":"Lange-Carter","year":"1993","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB34","doi-asserted-by":"crossref","first-page":"5291","DOI":"10.1073\/pnas.93.11.5291","article-title":"Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated 195-kDa protein with a large regulatory domain","volume":"93","author":"Xu","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB35","doi-asserted-by":"crossref","first-page":"11757","DOI":"10.1074\/jbc.270.20.11757","article-title":"Direct interaction between Ras and the kinase domain of mitogen-activated protein kinase kinase kinase (MEKK1)","volume":"270","author":"Russell","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB36","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1126\/science.8073291","article-title":"Ras-dependent growth factor regulation of MEK kinase in PC12 cells","volume":"265","author":"Lange-Carter","year":"1994","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB37","doi-asserted-by":"crossref","first-page":"12762","DOI":"10.1074\/jbc.271.22.12762","article-title":"Aggregation of the Fc\u03b5RI on mast cells stimulates c-Jun amino-terminal kinase activity","volume":"271","author":"Ishizuka","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB38","doi-asserted-by":"crossref","first-page":"8971","DOI":"10.1074\/jbc.271.15.8971","article-title":"Interaction between c-Rel and the mitogen activated protein kinase kinase kinase 1 signaling cascade in mediating \u03baB enhancer activation","volume":"271","author":"Meyer","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB39","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1126\/science.270.5244.2008","article-title":"Identification of a member of the MAPKKK family as a potential mediator of TGF-\u03b2 signal transduction","volume":"270","author":"Yamaguchi","year":"1995","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB40","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1126\/science.272.5265.1179","article-title":"TAB1: an activator of the TAK1 MAPKKK in TGF-\u03b2 signal transduction","volume":"272","author":"Shibuya","year":"1996","journal-title":"Science"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB41","doi-asserted-by":"crossref","first-page":"16802","DOI":"10.1016\/S0021-9258(19)89463-2","article-title":"Differential expression of a novel protein kinase in human lymphocytes","volume":"269","author":"Katz","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB42","doi-asserted-by":"crossref","first-page":"26690","DOI":"10.1074\/jbc.270.44.26690","article-title":"Identification and molecular cloning of a p21cdc42\/rac1 activated serine\/threonine kinase that is rapidly activated by thrombin in platelets","volume":"270","author":"Teo","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB43_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0092-8674(00)81371-9","article-title":"Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK\/SAPK MAP kinase cascade","volume":"87","author":"Lamarche","year":"1996","journal-title":"Cell"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB44","doi-asserted-by":"crossref","first-page":"25746","DOI":"10.1074\/jbc.271.42.25746","article-title":"Interaction of the Nck adapter protein with p21-activated kinase (PAK1)","volume":"271","author":"Bokoch","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB45","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0378-1119(95)00653-2","article-title":"Cloning and characterization of a member of the MST subfamily of Ste20-like kinases","volume":"167","author":"Creasy","year":"1995","journal-title":"Gene"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB46","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/j.1432-1033.1993.tb17810.x","article-title":"Identification of new family of human epithelial protein kinases containing two leucine\/isoleucine-zipper domains","volume":"213","author":"Dorow","year":"1993","journal-title":"Eur J Biochem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB47","first-page":"935","article-title":"PTK1, a novel protein kinase required for proliferation of human melanocytes","volume":"9","author":"Ezoe","year":"1994","journal-title":"Oncogene"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB48","doi-asserted-by":"crossref","first-page":"30808","DOI":"10.1016\/S0021-9258(18)47353-X","article-title":"Identification, molecular cloning, and characterization of dual leucine-zipper bearing kinase","volume":"269","author":"Holzman","year":"1994","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB49","first-page":"1447","article-title":"Cloning and characterization of MST, a novel (putative) serine\/threonine kinase with SH3 domain","volume":"10","author":"Katoh","year":"1995","journal-title":"Oncogene"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB50","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1006\/bbrc.1994.1972","article-title":"Cloning of a novel putative protein kinase having a leucine zipper domain from human brain","volume":"202","author":"Reddy","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB51","doi-asserted-by":"crossref","first-page":"21695","DOI":"10.1074\/jbc.270.37.21695","article-title":"Cloning and characterization of a human protein kinase with homology to Ste20","volume":"270","author":"Creasy","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB52","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1073\/pnas.90.6.2251","article-title":"Tumor progression locus 2 (Tpl-2) encodes a protein kinase involved in the progression of rodent T-cell lymphomas and in T-cell activation","volume":"90","author":"Patrios","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB53","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.1128\/MCB.11.8.4088","article-title":"Structure and transforming potential of the human cot oncogene encoding a putative protein kinase","volume":"11","author":"Miyoshi","year":"1991","journal-title":"Mol Cell Biol"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB54","doi-asserted-by":"crossref","first-page":"9755","DOI":"10.1073\/pnas.91.21.9755","article-title":"Tpl-2 acts in concert with Raf-1 to activate mitogen-activated protein kinase","volume":"91","author":"Patriotis","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB55","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/j.1460-2075.1996.tb00417.x","article-title":"Activation of MEK-1 and SEK-1 by Tpl-2 protoncoprotein, a novel MAP kinase kinase kinase","volume":"15","author":"Salmeron","year":"1996","journal-title":"EMBO J"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB56","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1002\/j.1460-2075.1996.tb00636.x","article-title":"Selective interaction of JNK protein kinase isoforms with transcription factors","volume":"15","author":"Gupta","year":"1996","journal-title":"EMBO J"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB57","doi-asserted-by":"crossref","first-page":"31607","DOI":"10.1074\/jbc.271.49.31607","article-title":"Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase","volume":"271","author":"Wang","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1016\/S0959-437X(97)80111-6_BIB58","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1126\/science.275.5296.90","article-title":"Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK\/JNK and p38 signaling pathways","volume":"257","author":"Ichijo","year":"1997","journal-title":"Science"}],"container-title":["Current Opinion in Genetics & Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X97801116?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0959437X97801116?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T12:51:29Z","timestamp":1680785489000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0959437X97801116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,2]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1997,2]]}},"alternative-id":["S0959437X97801116"],"URL":"https:\/\/doi.org\/10.1016\/s0959-437x(97)80111-6","relation":{},"ISSN":["0959-437X"],"issn-type":[{"value":"0959-437X","type":"print"}],"subject":[],"published":{"date-parts":[[1997,2]]}}}