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PMID: 7939666 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1.

Science (New York, N.Y.) ·Vol. 266 ·No. 5183 ·1994-10-14 ·Pages 285-8

Sun H, Tonks NK, Bar-Sagi D

Abstract

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, V12Ras. 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.

MeSH Terms

Animals Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors Cell Cycle Proteins Cell Line DNA/biosynthesis Dual Specificity Phosphatase 1 Enzyme Activation HeLa Cells Humans Immediate-Early Proteins/metabolism,pharmacology JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinases Molecular Sequence Data Mutation Phosphoprotein Phosphatases Protein Phosphatase 1 Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism Protein Tyrosine Phosphatases/metabolism,pharmacology Protein-Tyrosine Kinases/antagonists & inhibitors,metabolism Rats Resting Phase, Cell Cycle S Phase Signal Transduction Transfection ras Proteins/genetics,metabolism

Chemicals

Cell Cycle Proteins Immediate-Early Proteins DNA Protein-Tyrosine Kinases Protein Serine-Threonine Kinases Calcium-Calmodulin-Dependent Protein Kinases JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinases Phosphoprotein Phosphatases Protein Phosphatase 1 DUSP1 protein, human Dual Specificity Phosphatase 1 Dusp1 protein, rat Protein Tyrosine Phosphatases ras Proteins

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Sun H

Cold Spring Harbor Laboratory, NY 11724-2208.

Tonks N K

Bar-Sagi D

Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

0036-8075

DOI

10.1126/science.7939666

Published

1994-10-14

Pages

285-8

Language

English

Region

United States

NLM ID

0404511

Subset

Grants

NCI NIH HHS · CA53840 · United States

NCI NIH HHS · CA55360 · United States

External Links

PubMed source DOI: 10.1126/science.7939666 View journal details

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Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1.

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