scholarly journals TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity

2021 ◽  
Author(s):  
Wenyu Fu ◽  
Wenhuo Hu ◽  
Young-Su Yi ◽  
Aubryanna Hettinghouse ◽  
Guodong Sun ◽  
...  
Keyword(s):  
Signaling Complex ◽  
Macrophage Plasticity

scholarly journals Synergistic Interaction of MEK Kinase 2, c-Jun N-Terminal Kinase (JNK) Kinase 2, and JNK1 Results in Efficient and Specific JNK1 Activation

2000 ◽  
Vol 20 (7) ◽  
pp. 2334-2342 ◽  
Author(s):  
Jinke Cheng ◽  
Jianhua Yang ◽  
Ying Xia ◽  
Michael Karin ◽  
Bing Su
Keyword(s):  
Complex Formation ◽  
Molecular Basis ◽  
Synergistic Interaction ◽  
Specific Flow ◽  
Mitogen Activated Protein Kinases ◽  
Mapk Kinase ◽  
Signaling Complex ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Flow Of Information

ABSTRACT Mitogen-activated protein kinases (MAPKs) are activated through cascades or modules consisting of a MAPK, a MAPK kinase (MAPKK), and a MAPKK kinase (MAPKKK). Investigating the molecular basis of activation of the c-Jun N-terminal kinase (JNK) subgroup of MAPK by the MAPKKK MEKK2, we found that strong and specific JNK1 activation by MEKK2 was mediated by the MAPKK JNK kinase 2 (JNKK2) rather than by JNKK1 through formation of a tripartite complex consisting of MEKK2, JNKK2, and JNK1. No scaffold protein was required for the MEKK2-JNKK2-JNK1 tripartite-complex formation. Expression of JNK1, JNKK2, and MEKK2 significantly augmented the coprecipitation of, respectively, MEKK2-JNKK2, MEKK2-JNK1, and JNKK2-JNK1, indicating that the interaction of MEKK2, JNKK2, and JNK1 is synergistic. Finally, the JNK1 was activated more efficiently in the MEKK2-JNKK2-JNK1 complex than was the JNK1 excluded from the complex. Thus, formation of a signaling complex through synergistic interaction of a MAPKKK, a MAPKK, and a MAPK molecule like MEKK2-JNKK2-JNK1 is likely to be responsible for the efficient, specific flow of information via MAPK cascades.

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