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Zinc finger protein ZPR9 interacts with MPK38, an AMPK‐related serine/threonine kinase, and stimulates MPK38‐dependent ASK1‐, TGF‐β‐, and p53 function
Author(s) -
Ha Hyunjung,
Seong HyunA
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb185
Subject(s) - ask1 , activator (genetics) , ampk , protein kinase a , map kinase kinase kinase , serine , kinase , phosphorylation , threonine , chemistry , akt3 , cyclin dependent kinase 9 , microbiology and biotechnology , mitogen activated protein kinase kinase , c raf , map2k7 , biochemistry , cyclin dependent kinase 2 , biology , receptor
Murine protein serine‐threonine kinase 38 (MPK38) is a member of the AMP‐activated protein kinase (AMPK)‐related serine/threonine kinase family and plays a role in inducing ASK1‐, TGF‐β‐, and p53‐mediated activity. Here, zinc finger protein ZPR9 was found to be a positive regulator of MPK38. The redox‐dependent association of MPK38 and ZPR9 was mediated by cysteine residues present in each of these two proteins, Cys 269 and Cys 286 of MPK38 and Cys 305 and Cys 308 of ZPR9. MPK38 phosphorylated ZPR9 at Thr 252 , indicating ZPR9 as an endogenous substrate for MPK38. Expression of wild‐type ZPR9, but not the ZPR9 mutants C305S/C308S and T252A, enhanced MPK38‐induced ASK1, TGF‐β, and p53 function by stabilizing MPK38. Consistently, knockdown of endogenous ZPR9 using an inducible ZPR9 shRNA system showed an opposite trend and inhibited the MPK38‐induced ASK1, TGF‐β, and p53 function. These results suggest that ZPR9 functions as an activator in MPK38‐dependent ASK1‐, TGF‐β‐, and p53 signaling pathways. Support or Funding Information This work was supported by National Research Foundation of Korea Grant 2015R1A2A2A01006098