DOI: 10.1126/science.7811320. Activation of Raf as a Result of Recruitment to the Plasma Membrane

Activation of Raf as a Result of Recruitment to the Plasma Membrane

10.1126/science.7811320

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The small guanine nucleotide binding protein Ras participates in a growth promoting signal transduction pathway. The mechanism by which interaction of Ras with the protein kinase Raf leads to activation of Raf was studied. Raf was targeted to the plasma membrane by addition of the COOH-terminal localization signals of K-ras. This modified form of Raf (RafCAAX) was activated to the same extent as Raf coexpressed with oncogenic mutant Ras. Plasma membrane localization rather than farnesylation or the presence of the additional COOH-terminal sequence accounted for the activation of RafCAAX. The activation of RafCAAX was completely independent of Ras; it was neither potentiated by oncogenic mutant Ras nor abrogated by dominant negative Ras. Raf, once recruited to the plasma membrane, was not anchored there by Ras; most activated Raf in cells was associated with plasma membrane cytoskeletal elements, not the lipid bilayer. Thus, Ras functions in the activation of Raf by recruiting Raf to the plasma membrane where a separate, Ras-independent, activation of Raf occurs.

Bibliography

Stokoe, D., Macdonald, S. G., Cadwallader, K., Symons, M., & Hancock, J. F. (1994). Activation of Raf as a Result of Recruitment to the Plasma Membrane. Science, 264(5164), 1463â1467.

Authors 5

David Stokoe (first)
Susan G. Macdonald (additional)
Karen Cadwallader (additional)
Marc Symons (additional)
John F. Hancock (additional)

References 29 Referenced 777

10.1016/0092-8674(93)90146-H
Cadwallader, K., Molecular and Cellular Biology 14: 7 (1994). / Molecular and Cellular Biology (1994)
10.1126/science.8493579
10.1126/science.1411546
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10.1038/363045a0
EVAN, G.I., ISOLATION OF MONOCLONAL-ANTIBODIES SPECIFIC FOR HUMAN C-MYC PROTO-ONCOGENE PRODUCT, MOLECULAR AND CELLULAR BIOLOGY 5: 3610 (1985). / MOLECULAR AND CELLULAR BIOLOGY (1985)
FEIG, L.A., INHIBITION OF NIH-3T3 CELL-PROLIFERATION BY A MUTANT RAS PROTEIN WITH PREFERENTIAL AFFINITY FOR GDP, MOLECULAR AND CELLULAR BIOLOGY 8: 3235 (1988). / MOLECULAR AND CELLULAR BIOLOGY (1988)
FINNEY, R.E., ASSOCIATION OF PRAS AND PRAF-1 IN A COMPLEX CORRELATES WITH ACTIVATION OF A SIGNAL-TRANSDUCTION PATHWAY, CURRENT BIOLOGY 3: 805 (1993). (10.1016/0960-9822(93)90214-9) / CURRENT BIOLOGY (1993)
GRUSSENMEYER, T, COMPLEXES OF POLYOMA-VIRUS MEDIUM T-ANTIGEN AND CELLULAR PROTEINS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 82: 7952 (1985). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1985)
10.1016/0092-8674(89)90054-8
10.1016/0092-8674(90)90294-O
HANCOCK, J.F., A CAAX OR A CAAL MOTIF AND A 2ND SIGNAL ARE SUFFICIENT FOR PLASMA-MEMBRANE TARGETING OF RAS PROTEINS, EMBO JOURNAL 10: 4033 (1991). (10.1002/j.1460-2075.1991.tb04979.x) / EMBO JOURNAL (1991)
10.1016/0092-8674(92)90361-F
HUANG, DCS, PLASMA MEMBRANE-TARGETED RAS GTPASE-ACTIVATING PROTEIN IS A POTENT SUPPRESSOR OF P21(RAS) FUNCTION, MOLECULAR AND CELLULAR BIOLOGY 13: 2420 (1993). / MOLECULAR AND CELLULAR BIOLOGY (1993)
KOIDE, H, GTP-DEPENDENT ASSOCIATION OF RAF-1 WITH HA-RAS - IDENTIFICATION OF RAF AS A TARGET DOWNSTREAM OF RAS IN MAMMALIAN-CELLS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 8683 (1993). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1993)
10.1038/358417a0
10.1126/science.8385802
MACDONALD, S.G., RECONSTITUTION OF THE RAF-1-MEK-ERK SIGNAL-TRANSDUCTION PATHWAY IN-VITRO, MOLECULAR AND CELLULAR BIOLOGY 13: 6615 (1993). / MOLECULAR AND CELLULAR BIOLOGY (1993)
MACDONALD S.G. unpublished data.
10.1126/science.8503013
SAITO, Y, THE THREONINE RESIDUES IN MAP KINASE KINASE-1 PHOSPHORYLATED BY MAP KINASE IN-VITRO ARE ALSO PHOSPHORYLATED IN NERVE GROWTH FACTOR-STIMULATED RAT PHEOCHROMOCYTOMA (PC12) CELLS, FEBS LETTERS 341: 119 (1994). (10.1016/0014-5793(94)80252-1) / FEBS LETTERS (1994)
TRAVERSE, S, SPECIFIC ASSOCIATION OF ACTIVATED MAP KINASE KINASE KINASE (RAF) WITH THE PLASMA-MEMBRANES OF RAS-TRANSFORMED RETINAL CELLS, ONCOGENE 8: 3175 (1993). / ONCOGENE (1993)
10.1073/pnas.90.13.6213
10.1016/0092-8674(93)90307-C
10.1038/364352a0
WILLIAMS, N.G., BOTH P21(RAS) AND PP60(V-SRC) ARE REQUIRED, BUT NEITHER ALONE IS SUFFICIENT, TO ACTIVATE THE RAF-1 KINASE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 2922 (1992). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1992)
WILLUMSEN, B.M., THE P21 RAS C-TERMINUS IS REQUIRED FOR TRANSFORMATION AND MEMBRANE ASSOCIATION, NATURE 310: 583 (1984). (10.1038/310583a0) / NATURE (1984)
10.1038/364308a0

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 8:01 p.m.)
Deposited	1 year, 7 months ago (Jan. 15, 2024, 12:35 a.m.)
Indexed	1 week, 1 day ago (Aug. 21, 2025, 12:43 p.m.)
Issued	31 years, 2 months ago (June 3, 1994)
Published	31 years, 2 months ago (June 3, 1994)
Published Print	31 years, 2 months ago (June 3, 1994)

Funders 0

None

BibTeX

@article{Stokoe_1994, title={Activation of Raf as a Result of Recruitment to the Plasma Membrane}, volume={264}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.7811320}, DOI={10.1126/science.7811320}, number={5164}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Stokoe, David and Macdonald, Susan G. and Cadwallader, Karen and Symons, Marc and Hancock, John F.}, year={1994}, month=jun, pages={1463–1467} }

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