title: ERK1 Directly Interacts With JNK1 Leading to Regulation of JNK1/c-Jun Activity and Cell Transformation.
abstract: ERK1 and ERK2 share a great deal of homology and have been presumed to have similar functions. Available antibodies recognize both isoforms making the elucidation of functional differences challenging. Mitogen-activated protein (MAP) kinase networks are commonly depicted in the literature as linear and sequential phosphorylation cascades; however, the activation of these pathways is not mutually exclusive. Little doubt exists that MAP kinases engage in crosstalk, but the extent or the direct effect of these "conversations" is unclear. Here, we report the possible points of direct interaction as "crosstalk" points between ERK1 and JNK1 and a potential mechanism for ERK1 function in repressing Ras/JNK-mediated cell transformation. ERK1, but not ERK2, directly interacts with and antagonizes JNK1 phosphorylation and activity, resulting in suppression of neoplastic cell transformation mediated by the Ras/JNK/c-Jun signaling pathway. Interestingly, ERK1 phosphorylation was increased in normal tissues compared to liver cancer tissues. Furthermore, predominant JNK/c-Jun activation was observed in liver cancer tissues. These phenomena can provide evidence for the existence of a functional association between ERK and JNK signaling pathways during in vivo tumorigenesis. Overall, our findings provide new evidence supporting the paradigm of an ERK1/JNK1 antagonistic interaction as a novel mechanism of trans-regulation between different MAP kinase signaling modules. J. Cell. Biochem. 118: 2357-2370, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
authors.forename: Bong Seok
authors.initials: BS
authors.lastname: Kang
authors.affiliation: Bio-Medical Research Institute, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.|Department of Surgery, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
authors.forename: Yoon Jin
authors.initials: YJ
authors.lastname: Hwang
authors.affiliation: The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, Minnesota, 55912.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D051379:Mice; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering; D020349:Surface Plasmon Resonance; D018808:Transcription Factor AP-1
chemical_list: D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8
keywords: CARCINOGENESIS; CELL TRANSFORMATION; CROSSTALK; ERK; JNK; PROTEIN INTERACTION