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PMID: 8390681 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Raf-1 and p21v-ras cooperate in the activation of mitogen-activated protein kinase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 12 ·1993-06-15 ·Pages 5772-6

Williams NG, Paradis H, Agarwal S, Charest DL, Pelech SL, Roberts TM

Abstract

Mitogen-activated protein (MAP) kinases Raf-1, pp60src, and p21ras all play important roles in the transfer of signals from the cell surface to the nucleus. We have used the baculovirus/Sf9 insect cell system to elucidate the regulatory relationships between pp60v-src, p21v-ras, MAP kinase (p44erk1/mapk), and Raf-1. In Sf9 cells, p44erk1/mapk is activated by coexpression with either v-Raf or a constitutively activated form of Raf-1 (Raf22W). In contrast, p44erk1/mapk is activated to only a limited extent by coexpression with either Raf-1 or p21v-ras alone. This activation of p44erk1/mapk is greatly enhanced by coexpression with both p21v-ras and Raf-1. Since we have previously shown that p21v-ras stimulates Raf-1 activity, the activation of p44erk1/mapk by p21v-ras may occur exclusively via a Raf-1-dependent pathway. However, a dominant-inhibitory mutant of Raf-1 (Raf301) does not block the activation of p44erk1/mapk by p21-v-ras. Further, pp60v-src, which activates Raf-1 at least as effectively as p21v-ras, fails to enhance p44erk1/mapk activity greatly when coexpressed with Raf-1. These data suggest that activation of p44erk1/mapk by p21v-ras may occur via both Raf-1-dependent and Raf-1-independent pathways.

Related Genes
c-raf-1
MeSH Terms
Amino Acid Sequence Animals Antibodies Antibodies, Monoclonal Antigen-Antibody Complex/metabolism Baculoviridae/genetics Calcium-Calmodulin-Dependent Protein Kinases Cell Line Cloning, Molecular Enzyme Activation Genetic Vectors Molecular Sequence Data Moths Mutagenesis Oncogene Protein p21(ras)/metabolism Protein Kinases/metabolism Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-raf Rats Recombinant Proteins/metabolism Restriction Mapping Transfection
Chemicals
Antibodies Antibodies, Monoclonal Antigen-Antibody Complex Proto-Oncogene Proteins Recombinant Proteins Protein Kinases Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-raf Calcium-Calmodulin-Dependent Protein Kinases Oncogene Protein p21(ras)
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Williams N G
Dana-Farber Cancer Institute, Boston, MA.
Paradis H
Agarwal S
Charest D L
Pelech S L
Roberts T M
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37 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.12.5772
Published
1993-06-15
Pages
5772-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46804
Subset
IM
Grants
NCI NIH HHS · CA43803 · United States
NICHD NIH HHS · HD24926 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.12.5772 PMC Full Text View journal details
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