Induction of mitogen-activated protein kinase phosphatase 1 by the stress-activated protein kinase signaling pathway but not by extracellular signal-regulated kinase in fibroblasts. J Biol Chem 1996 Jan 12;271(2):639-42
Date
01/12/1996Pubmed ID
8557667DOI
10.1074/jbc.271.2.639Scopus ID
2-s2.0-0030046479 (requires institutional sign-in at Scopus site) 153 CitationsAbstract
The intracellular mechanisms involved in the activation of extracellular signal-regulated kinase (ERK) are relatively well understood. However, the intracellular signaling pathways which regulate the termination of ERK activity remain to be elucidated. Mitogen-activated protein kinase phosphatase 1 (MKP-1) has been shown to dephosphorylate and inactivate ERK in vitro and in vivo. In the present study, we show in NIH3T3 fibroblasts that activation of the stress-activated protein kinase (SAPK) pathway by either specific extracellular stress stimuli or via induction of MEKK, an upstream kinase of SAPK, results in MKP-1 gene expression. In contrast, selective stimulation of the ERK pathway by 12-O-tetradecanoylphorbol-13-acetate or following expression of constitutively active MEK, the upstream dual specificity kinase of ERK did not induce the transcription of MKP-1. Hence, these findings demonstrate the existence of cross-talk between the ERK and SAPK signaling cascades since activation of SAPK induced the expression of MKP-1 that can inactivate ERK. This mechanism may modulate the cellular response to stimuli which employ the SAPK signal transduction pathway.
Author List
Bokemeyer D, Sorokin A, Yan M, Ahn NG, Templeton DJ, Dunn MJAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3T3 CellsAnimals
Cell Cycle Proteins
Dual Specificity Phosphatase 1
Enzyme Activation
Extracellular Space
Gene Expression Regulation, Enzymologic
Immediate-Early Proteins
Mice
Mutation
Phosphoprotein Phosphatases
Protein Kinases
Protein Phosphatase 1
Protein Tyrosine Phosphatases
Signal Transduction
