Inhibition of Ras-Induced DNA Synthesis by Expression of the Phosphatase MKP-1

Mitogen-activated protein kinases (MAP kinases) are common components of signaling pathways induced by diverse growth stimuli. Although the guanidine nucleotide-binding Ras proteins are known to be upstream activators of MAP kinases, the extent to which MAP kinases directly contribute to the mitogen...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1994-10, Vol.266 (5183), p.285-288
Main Authors: Sun, Hong, Tonks, Nicholas K., Bar-Sagi, Dafna
Format: Article
Language:English
Subjects:
3T3 cells
Animals
Antibodies
Base Sequence
Biological and medical sciences
Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors
Cell cycle
Cell Cycle Proteins
Cell Line
Cell physiology
Delta cells
DNA
DNA - biosynthesis
DNA mapping
Dual Specificity Phosphatase 1
Enzyme Activation
Fundamental and applied biological sciences. Psychology
HeLa Cells
Humans
Immediate-Early Proteins - metabolism
Immediate-Early Proteins - pharmacology
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinases
Molecular and cellular biology
Molecular Sequence Data
Mutation
Phosphatases
Phosphoprotein Phosphatases
Physiological aspects
Plasmids
Protein kinases
Protein Phosphatase 1
Protein Tyrosine Phosphatases - metabolism
Protein Tyrosine Phosphatases - pharmacology
Protein-Serine-Threonine Kinases - antagonists & inhibitors
Protein-Serine-Threonine Kinases - metabolism
Protein-Tyrosine Kinases - antagonists & inhibitors
Protein-Tyrosine Kinases - metabolism
ras Proteins - genetics
ras Proteins - metabolism
Rats
Resting Phase, Cell Cycle
S Phase
Signal Transduction
Transfection
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Summary:Mitogen-activated protein kinases (MAP kinases) are common components of signaling pathways induced by diverse growth stimuli. Although the guanidine nucleotide-binding Ras proteins are known to be upstream activators of MAP kinases, the extent to which MAP kinases directly contribute to the mitogenic effect of Ras is as yet undefined. In this study, inhibition of MAP kinases by the MAP kinase phosphatase MKP-1 blocked the induction of DNA synthesis in quiescent rat embryonic fibroblast REF-52 cells by an activated mutant of Ras, V$^{12}$Ras. These results suggest an essential role for activation of MAP kinases in the transition from the quiescent to the DNA replication phase of the eukaryotic cell cycle.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.7939666