Differential requirement of MKK4 and MKK7 in JNK activation by distinct scaffold proteins.
Different scaffold proteins play distinct roles in various signaling pathways by recruiting different downstream molecules. Here, using MKK4(-/-) and MKK4(-/-)/7(-/-) murine embryonic fibroblast cells, we examined differential employment of MKK4 and MKK7 by scaffold proteins Axin, Dvl, and Epstein-Barr virus latent membrane protein-1 (LMP-1) in mediating JNK activation. We present evidence that Axin depends mainly on MKK7 for activation of JNK, while Dvl depends almost equally on MKK4 and MKK7 for JNK activation, In contrast, LMP-1-induced JNK activation is primarily dependent on MKK4. Our results demonstrate that Axin, Dvl, and LMP-1 differentially utilize MKK4 and MKK7 for JNK activation.
Zou
Haiying
H
Department of Biomedical Sciences, The Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Fujian 361005, China.
Li
Qinxi
Q
Lin
Sheng-Cai
SC
Wu
Zhenguo
Z
Han
Jiahuai
J
Ye
Zhiyun
Z
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D060466:Axin Protein; D002460:Cell Line; D000072261:Dishevelled Proteins; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D048688:MAP Kinase Kinase 7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D012097:Repressor Proteins / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D000072261:Dishevelled Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014763:Viral Matrix Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482562:Map2k4 protein, mouse; C482570:Map2k7 protein, mouse