Coordinated Regulation of MAPK and STAT3 Proteins on TNF-? Transcription Activity
- VernacularTitle:STAT3与MAPK蛋白协同调节肿瘤坏死因子-?转录活性
- Author:
Liping YANG
;
Yongming YAO
;
Jieping LI
;
Qinong YE
;
Zhiyong SHENG
- Publication Type:Journal Article
- Keywords:
signal transducer and activator of transcription 3(STAT3), p38 mitogen-activated protein kinase, extracellular-signal regulated protein kinase, tumor necrosis factor-?
- From:
Progress in Biochemistry and Biophysics
2006;0(08):-
- CountryChina
- Language:Chinese
-
Abstract:
In order to investigate if there exists interaction between mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) protein, and how the interaction regulates tumor necrosis factor-? (TNF-?) transcription activity, the human p38 and extracellular-signal regulated protein kinase 2 (ERK2) genes were amplified from human flag-p38 and flag-ERK2 by polymerase chain reaction (PCR) and cloned into pcDNA3-HA. Protein expression of the plasmids was examined by Western blotting. Co-immunoprecipitation was used to identify if there exists interaction between MAPK and STAT3 proteins. If the interaction was approved to be true, report gene system was applied to find how the interaction affect transcriptional expression of TNF-?. After STAT3 pathway was inhibited by RNA interfering, the action on TNF-? activity was determined. The results of DNA sequencing and enzyme digestion showed that the cloned p38 and ERK2 genes were correct, to be 1 080 bp or so. p38 and ERK2 proteins were expressed in 293T cell to be approximately 40 ku. Co-immunoprecipitation data showed that p38 and ERK2 proteins integrated with STAT3 protein in vivo. TNF-? reporter gene activity results found that protein complex of p38-STAT3 and ERK2-STAT3 coordinately increased TNF-? activity. After STAT3 was interfered, the TNF-? activity markedly decreased. These data indicated that there exists interaction between p38 and STAT3 protein, ERK2 and STAT3 protein. The complex of the proteins can coordinately regulate TNF-? expression. After interfereing STAT3 pathway, the coordinated action on TNF-? transcription activity might be obviously reduced.
