MAPK Kinase Kinase Regulation of SAPK/JNK Pathways

Author(s):  
Lisa Stalheim ◽  
Gary L. Johnson
2000 ◽  
Vol 20 (7) ◽  
pp. 2334-2342 ◽  
Author(s):  
Jinke Cheng ◽  
Jianhua Yang ◽  
Ying Xia ◽  
Michael Karin ◽  
Bing Su

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.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 832
Author(s):  
Damian Tanski ◽  
Agnieszka Skowronska ◽  
Malgorzata Tanska ◽  
Ewa Lepiarczyk ◽  
Mariusz T. Skowronski

Aquaporins (AQPs) are integral membrane proteins, which play an important role in water homeostasis in the uterus. According to the literature, the expression of aquaporins in reproductive structures depends on the local hormonal milieu. The current study investigated the effect of selected PKA kinase inhibitor H89 and MAPK kinase inhibitor PD98059, on the expression of AQP1, 2, 5, and 7, and steroid hormones (E2), progesterone (P4), and arachidonic acid (AA) in the porcine endometrium on days 18–20 and 2–4 of the estrous cycle (the follicular phase where estrogen and follicle-stimulating hormone (FSH) are secreted increasingly in preparation for estrus and the luteal phase where the ovarian follicles begin the process of luteinization with the formation of the corpus luteum and progesterone secretion, respectively). The luminal epithelial cells were incubated in vitro in the presence of the aforementioned factors. The expression of mRNA was determined by the quantitative real-time PCR technique. In general, in Experiment 1, steroid hormones significantly increased expression of AQP1, 2, and 5 while arachidonic acid increased expression of AQP2 and AQP7. On the other hand, MAPK kinase inhibitor significantly decreased the expression of AQP1 and 5. In Experiment 2, E2, P4, or AA combined with kinase inhibitors differentially affected on AQPs expression. E2 in combination with PKA inhibitor significantly decreased expression of AQP1 but E2 or P4 combined with this inhibitor increased the expression of AQP5 and 7. On the contrary, E2 with PD98059 significantly increased AQP5 and AQP7 expression. Progesterone in combination with MAPK kinase inhibitor significantly downregulated the expression of AQP5 and upregulated AQP7. Arachidonic acid mixed with H89 or PD98059 caused a decrease in the expression of AQP5 and an increase of AQP7. The obtained results indicate that estradiol, progesterone, and arachidonic acid through PKA and MAPK signaling pathways regulate the expression of AQP1 and AQP5 in the porcine luminal epithelial cells in the periovulatory period.


Nature ◽  
10.1038/20951 ◽  
1999 ◽  
Vol 399 (6735) ◽  
pp. 479-483 ◽  
Author(s):  
Reiko Sugiura ◽  
Takashi Toda ◽  
Susheela Dhut ◽  
Hisato Shuntoh ◽  
Takayoshi Kuno ◽  
...  
Keyword(s):  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Dorota A. Rzechonek ◽  
Alison M. Day ◽  
Janet Quinn ◽  
Aleksandra M. Mirończuk

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