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Science 3 June 1994:
Vol. 264. no. 5164, pp. 1463 - 1467
DOI: 10.1126/science.7811320
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Articles

Science, Vol 264, Issue 5164, 1463-1467
Copyright © 1994 by American Association for the Advancement of Science

articles

Activation of Raf as a result of recruitment to the plasma membrane

D Stokoe, SG Macdonald, K Cadwallader, M Symons, and JF Hancock

ONXY Pharmaceuticals, Richmond, CA 94806.

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.


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   Abstract »    Full Text »
c-raf-1 Depletion and Tumor Responses in Patients Treated with the c-raf-1 Antisense Oligodeoxynucleotide ISIS 5132 (CGP 69846A).
P. J. O'Dwyer, J. P. Stevenson, M. Gallagher, A. Cassella, I. Vasilevskaya, B. P. Monia, J. Holmlund, F. A. Dorr, and K.-S. Yao (1999)
Clin. Cancer Res. 5, 3977-3982
   Abstract »    Full Text »    PDF »
RIP2 Is a Raf1-activated Mitogen-activated Protein Kinase Kinase.
T. A. Navas, D. T. Baldwin, and T. A. Stewart (1999)
J. Biol. Chem. 274, 33684-33690
   Abstract »    Full Text »    PDF »
Ras Protein Farnesyltransferase: A Strategic Target for Anticancer Therapeutic Development.
E. K. Rowinsky, J. J. Windle, and D. D. Von Hoff (1999)
J. Clin. Oncol. 17, 3631-3652
   Abstract »    Full Text »    PDF »
Distinct Domains of Mouse Dishevelled Are Responsible for the c-Jun N-terminal Kinase/Stress-activated Protein Kinase Activation and the Axis Formation in Vertebrates.
T. Moriguchi, K. Kawachi, S. Kamakura, N. Masuyama, H. Yamanaka, K. Matsumoto, A. Kikuchi, and E. Nishida (1999)
J. Biol. Chem. 274, 30957-30962
   Abstract »    Full Text »    PDF »
Decreased Sensitivity to 1-O-Octadecyl-2-O-methyl-glycerophosphocholine in MCF-7 Cells Adapted for Serum-free Growth Correlates with Constitutive Association of Raf-1 with Cellular Membranes.
P. Samadder and G. Arthur (1999)
Cancer Res. 59, 4808-4815
   Abstract »    Full Text »    PDF »
M-Ras, a Widely Expressed 29-kD Homologue of p21 Ras: Expression of a Constitutively Active Mutant Results in Factor-Independent Growth of an Interleukin-3-Dependent Cell Line.
G. R.A. Ehrhardt, K. B. Leslie, F. Lee, J. S. Wieler, and J. W. Schrader (1999)
Blood 94, 2433-2444
   Abstract »    Full Text »    PDF »
Association of the Ras to Mitogen-activated Protein Kinase Signal Transduction Pathway with Microfilaments. EVIDENCE FOR A p185neu-CONTAINING CELL SURFACE SIGNAL TRANSDUCTION PARTICLE LINKING THE MITOGENIC PATHWAY TO A MEMBRANE-MICROFILAMENT ASSOCIATION SITE.
C. A. C. Carraway, M. E. Carvajal, and K. L. Carraway (1999)
J. Biol. Chem. 274, 25659-25667
   Abstract »    Full Text »    PDF »
The Strength of Interaction at the Raf Cysteine-Rich Domain Is a Critical Determinant of Response of Raf to Ras Family Small GTPases.
T. Okada, C.-D. Hu, T.-G. Jin, K.-i. Kariya, Y. Yamawaki-Kataoka, and T. Kataoka (1999)
Mol. Cell. Biol. 19, 6057-6064
   Abstract »    Full Text »    PDF »
Short-Term Pravastatin Mediates Growth Inhibition and Apoptosis, Independently of Ras, via the Signaling Proteins p27Kip1 and PI3 Kinase.
R. H. WEISS, A. RAMIREZ, and A. JOO (1999)
J. Am. Soc. Nephrol. 10, 1880-1890
   Abstract »    Full Text »
Design, total chemical synthesis, and binding properties of a [Leu-91-N1-methyl-7-azaTrp]Ras-binding domain of c-Raf-1.
J. R. Sydor, C. Herrmann, S. B. H. Kent, R. S. Goody, and M. Engelhard (1999)
PNAS 96, 7865-7870
   Abstract »    Full Text »    PDF »
Phase I Clinical/Pharmacokinetic and Pharmacodynamic Trial of the c-raf-1 Antisense Oligonucleotide ISIS 5132 (CGP 69846A).
J. P. Stevenson, K.-S. Yao, M. Gallagher, D. Friedland, E. P. Mitchell, A. Cassella, B. Monia, T. J. Kwoh, R. Yu, J. Holmlund, et al. (1999)
J. Clin. Oncol. 17, 2227
   Abstract »    Full Text »    PDF »
The Ankyrin Repeat-containing Adaptor Protein Tvl-1 Is a Novel Substrate and Regulator of Raf-1.
J.-H. Lin, A. Makris, C. McMahon, S. E. Bear, C. Patriotis, V. R. Prasad, R. Brent, E. A. Golemis, and P. N. Tsichlis (1999)
J. Biol. Chem. 274, 14706-14715
   Abstract »    Full Text »    PDF »
16K Human Prolactin Inhibits Vascular Endothelial Growth Factor-Induced Activation of Ras in Capillary Endothelial Cells.
G. D’Angelo, J.-F. Martini, T. Iiri, W. J. Fantl, J. Martial, and R. I. Weiner (1999)
Mol. Endocrinol. 13, 692-704
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The Extracellular Domain of the Saccharomyces cerevisiae Sln1p Membrane Osmolarity Sensor Is Necessary for Kinase Activity.
D. B. Ostrander and J. A. Gorman (1999)
J. Bacteriol. 181, 2527-2534
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Identification and Characterization of Potential Effector Molecules of the Ras-related GTPase Rap2.
V. Nancy, R. M. F. Wolthuis, M.-F. de Tand, I. Janoueix-Lerosey, J. L. Bos, and J. de Gunzburg (1999)
J. Biol. Chem. 274, 8737-8745
   Abstract »    Full Text »    PDF »
KSR-1 Binds to G-protein beta gamma Subunits and Inhibits beta gamma -induced Mitogen-activated Protein Kinase Activation.
B. Bell, H. Xing, K. Yan, N. Gautam, and A. J. Muslin (1999)
J. Biol. Chem. 274, 7982-7986
   Abstract »    Full Text »    PDF »


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