Dual specificity phosphatase (DUSP)-4 is induced by platelet-derived growth factor -BB in an Erk1/2-, STAT3- and p53-dependent manner

Runting Yin; Glenda Eger; Niki Sarri; Charlotte Rorsman; Carl-Henrik Heldin; Johan Lennartsson

doi:10.1016/j.bbrc.2019.09.014

Dual specificity phosphatase (DUSP)-4 is induced by platelet-derived growth factor -BB in an Erk1/2-, STAT3- and p53-dependent manner

Biochem Biophys Res Commun. 2019 Nov 12;519(3):469-474. doi: 10.1016/j.bbrc.2019.09.014. Epub 2019 Sep 13.

Authors

Runting Yin¹, Glenda Eger², Niki Sarri³, Charlotte Rorsman², Carl-Henrik Heldin⁴, Johan Lennartsson⁵

Affiliations

¹ Department of Cardiology, Affiliated Hospital of Jiangsu University, ZhenJiang, 212001, Jiangsu, China; Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden. Electronic address: yinrunting@126.com.
² Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden.
³ Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, SE-751 23, Uppsala, Sweden.
⁴ Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, SE-751 23, Uppsala, Sweden.
⁵ Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden; Department of Pharmaceutical Biosciences, Uppsala University, Biomedical Center, Box 591, SE-751 24, Uppsala, Sweden.

PMID: 31526568
DOI: 10.1016/j.bbrc.2019.09.014

Abstract

Dual specificity phosphatase (DUSP) 4 has been described as a negative regulator of MAP kinase signaling, in particular for the ERK1/2 and JNK pathways. We found that DUSP4 expression was upregulated in response to prolonged platelet-derived growth factor (PDGF)-BB stimulation. The PDGF-BB-induced DUSP4 expression was dependent on ERK1/2, STAT3 and p53. We found that inhibition of ERK1/2 effectively reduced DUSP4 mRNA levels, whereas STAT3 was necessary for maintaining p53 expression. p53 has binding sites in the DUSP4 promoter and was found to promote DUSP4 expression.

Keywords: DUSP4; Erk1/2; Multifactor regulation; PDGF; STAT3; p53.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Becaplermin / pharmacology*
Cells, Cultured
Dual-Specificity Phosphatases / genetics*
Dual-Specificity Phosphatases / metabolism
Fibroblasts / cytology
Fibroblasts / drug effects*
Fibroblasts / metabolism
Gene Expression Regulation, Enzymologic / drug effects*
Humans
Microscopy, Fluorescence
Mitogen-Activated Protein Kinase 1 / genetics
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / genetics
Mitogen-Activated Protein Kinase 3 / metabolism
Mitogen-Activated Protein Kinase Phosphatases / genetics*
Mitogen-Activated Protein Kinase Phosphatases / metabolism
RNA Interference
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects
Signal Transduction / genetics
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism
Up-Regulation / drug effects*

Substances

STAT3 Transcription Factor
STAT3 protein, human
Tumor Suppressor Protein p53
Becaplermin
MAPK3 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase Phosphatases
DUSP4 protein, human
Dual-Specificity Phosphatases