| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
A key event for Ras transformation involves the direct physical
association between Ras and the Raf-1 kinase. This interaction promotes
both Raf translocation to the plasma membrane and activation of Raf
kinase activity. Although substantial experimental evidence has
demonstrated that Raf residues 51-131 alone are sufficient for
Ras binding, conflicting observations have suggested that the Raf
cysteine-rich domain (residues 139-184) may also be important for
interaction with Ras. To clarify the role of the Raf cysteine-rich
domain in Ras-Raf binding, we have compared the ability of two distinct
Raf fragments to interact with Ras using both in vitro Ras
binding and in vivo Ras inhibition assays. First, we
determined that both Raf sequences 2-140 and 139-186
(designated Raf-Cys) showed preferential binding to active, GTP-bound
Ras in vitro. Second, we observed that Raf-Cys antagonized
oncogenic Ras(Q61L)-mediated transactivation of Ras-responsive elements
and focus-forming activity in NIH 3T3 cells and insulin-induced
germinal vesicle breakdown in Xenopus laevis oocytes in
vivo. This inhibitory activity suggests that Raf-Cys can interact
with Ras in vivo. Taken together, these results suggest that
Ras interaction with two distinct domains of Raf-1 may be important in
Ras-mediated activation of Raf kinase activity.
Volume 270,
Number 17,
Issue of April 28, pp. 9809-9812, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. D. Vos, A. Dallol, K. Eckfeld, N. P. C. Allen, H. Donninger, L. B. Hesson, D. Calvisi, F. Latif, and G. J. Clark The RASSF1A Tumor Suppressor Activates Bax via MOAP-1 J. Biol. Chem., February 24, 2006; 281(8): 4557 - 4563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Beeram, A. Patnaik, and E. K. Rowinsky Raf: A Strategic Target for Therapeutic Development Against Cancer J. Clin. Oncol., September 20, 2005; 23(27): 6771 - 6790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Beazely, J. K. Alan, and V. J. Watts Protein Kinase C and Epidermal Growth Factor Stimulation of Raf1 Potentiates Adenylyl Cyclase Type 6 Activation in Intact Cells Mol. Pharmacol., January 1, 2005; 67(1): 250 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Huntington, J. M. Shields, C. J. Der, C. A. Wyatt, U. Benbow, C. L. Slingluff Jr., and C. E. Brinckerhoff Overexpression of Collagenase 1 (MMP-1) Is Mediated by the ERK Pathway in Invasive Melanoma Cells: ROLE OF BRAF MUTATION AND FIBROBLAST GROWTH FACTOR SIGNALING J. Biol. Chem., August 6, 2004; 279(32): 33168 - 33176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jirakulaporn and A. J. Muslin Cation Diffusion Facilitator Proteins Modulate Raf-1 Activity J. Biol. Chem., June 25, 2004; 279(26): 27807 - 27815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Lancet and J. E. Karp Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy Blood, December 1, 2003; 102(12): 3880 - 3889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Czyzyk, J. L. Brogdon, A. Badou, O. Henegariu, P. Preston Hurlburt, R. Flavell, and K. Bottomly Activation of CD4 T cells by Raf-independent effectors of Ras PNAS, May 13, 2003; 100(10): 6003 - 6008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. GOUNI-BERTHOLD and A. SACHINIDIS Does the coronary risk factor low density lipoprotein alter growth and signaling in vascular smooth muscle cells? FASEB J, October 1, 2002; 16(12): 1477 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Bondeva, A. Balla, P. Varnai, and T. Balla Structural Determinants of Ras-Raf Interaction Analyzed in Live Cells Mol. Biol. Cell, July 1, 2002; 13(7): 2323 - 2333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Booden, S. L. Campbell, and C. J. Der Critical but Distinct Roles for the Pleckstrin Homology and Cysteine-Rich Domains as Positive Modulators of Vav2 Signaling and Transformation Mol. Cell. Biol., April 15, 2002; 22(8): 2487 - 2497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, R. T. Waldron, A. Dhaka, A. Patel, M. M. Riley, E. Rozengurt, and J. Colicelli The RAS Effector RIN1 Directly Competes with RAF and Is Regulated by 14-3-3 Proteins Mol. Cell. Biol., February 1, 2002; 22(3): 916 - 926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Luttrell, F. L. Roudabush, E. W. Choy, W. E. Miller, M. E. Field, K. L. Pierce, and R. J. Lefkowitz Activation and targeting of extracellular signal-regulated kinases by beta -arrestin scaffolds PNAS, February 15, 2001; (2001) 41604898. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y. Takai, T. Sasaki, and T. Matozaki Small GTP-Binding Proteins Physiol Rev, January 1, 2001; 81(1): 153 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gupta, R. Plattner, C. J. Der, and E. J. Stanbridge Dissection of Ras-Dependent Signaling Pathways Controlling Aggressive Tumor Growth of Human Fibrosarcoma Cells: Evidence for a Potential Novel Pathway Mol. Cell. Biol., December 15, 2000; 20(24): 9294 - 9306. [Abstract] [Full Text]
|
|
|
|
|
|
J. W. Ramos, P. E. Hughes, M. W. Renshaw, M. A. Schwartz, E. Formstecher, H. Chneiweiss, and M. H. Ginsberg Death Effector Domain Protein PEA-15 Potentiates Ras Activation of Extracellular Signal Receptor-activated Kinase by an Adhesion-independent Mechanism Mol. Biol. Cell, September 1, 2000; 11(9): 2863 - 2872. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. A. Sheta, M. A. Harding, M. R. Conaway, and D. Theodorescu Focal Adhesion Kinase, Rap1, and Transcriptional Induction of Vascular Endothelial Growth Factor J Natl Cancer Inst, July 5, 2000; 92(13): 1065 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-S. Schmid, W. M. Pruitt, and P. F. Maness A MAP Kinase-Signaling Pathway Mediates Neurite Outgrowth on L1 and Requires Src-Dependent Endocytosis J. Neurosci., June 1, 2000; 20(11): 4177 - 4188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Shima, T. Okada, M. Kido, H. Sen, Y. Tanaka, M. Tamada, C.-D. Hu, Y. Yamawaki-Kataoka, K.-i. Kariya, and T. Kataoka Association of Yeast Adenylyl Cyclase with Cyclase-Associated Protein CAP Forms a Second Ras-Binding Site Which Mediates Its Ras-Dependent Activation Mol. Cell. Biol., January 1, 2000; 20(1): 26 - 33. [Abstract] [Full Text]
|
|
|
|
|
|
A. Rebollo and C. Martinez-A Ras Proteins: Recent Advances and New Functions Blood, November 1, 1999; 94(9): 2971 - 2980. [Full Text] [PDF]
|
|
|
|
|
|
T. Okada, C.-D. Hu, T.-G. Jin, K.-i. Kariya, Y. Yamawaki-Kataoka, and T. Kataoka The Strength of Interaction at the Raf Cysteine-Rich Domain Is a Critical Determinant of Response of Raf to Ras Family Small GTPases Mol. Cell. Biol., September 1, 1999; 19(9): 6057 - 6064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Lin, A. Makris, C. McMahon, S. E. Bear, C. Patriotis, V. R. Prasad, R. Brent, E. A. Golemis, and P. N. Tsichlis The Ankyrin Repeat-containing Adaptor Protein Tvl-1 Is a Novel Substrate and Regulator of Raf-1 J. Biol. Chem., May 21, 1999; 274(21): 14706 - 14715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-F. Yan, J. Lu, Y. S. Zou, J. Soh-Won, D. M. Cohen, P. M. Buttrick, D. R. Cooper, S. F. Steinberg, N. Mackman, D. J. Pinsky, et al. Hypoxia-associated Induction of Early Growth Response-1 Gene Expression J. Biol. Chem., May 21, 1999; 274(21): 15030 - 15040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Topham and S. M. Prescott Mammalian Diacylglycerol Kinases, a Family of Lipid Kinases with Signaling Functions J. Biol. Chem., April 23, 1999; 274(17): 11447 - 11450. [Full Text] [PDF]
|
|
|
|
|
|
C.-D. Hu, K.-i. Kariya, T. Okada, X. Qi, C. Song, and T. Kataoka Effect of Phosphorylation on Activities of Rap1A to Interact with Raf-1 and to Suppress Ras-dependent Raf-1 Activation J. Biol. Chem., January 1, 1999; 274(1): 48 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Giglione and A. Parmeggiani Raf-1 Is Involved in the Regulation of the Interaction between Guanine Nucleotide Exchange Factor and Ha-Ras. EVIDENCES FOR A FUNCTION OF Raf-1 AND PHOSPHATIDYLINOSITOL 3-KINASE UPSTREAM TO Ras J. Biol. Chem., December 25, 1998; 273(52): 34737 - 34744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Daub, J. Jöckel, T. Quack, C. K. Weber, F. Schmitz, U. R. Rapp, A. Wittinghofer, and C. Block The RafC1 Cysteine-Rich Domain Contains Multiple Distinct Regulatory Epitopes Which Control Ras-Dependent Raf Activation Mol. Cell. Biol., November 1, 1998; 18(11): 6698 - 6710. [Abstract] [Full Text]
|
|
|
|
|
|
A. K. Howe and R. L. Juliano Distinct Mechanisms Mediate the Initial and Sustained Phases of Integrin-mediated Activation of the Raf/MEK/Mitogen-activated Protein Kinase Cascade J. Biol. Chem., October 16, 1998; 273(42): 27268 - 27274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sanchez-Mejorada and C. Rosales Fcgamma Receptor-mediated Mitogen-activated Protein Kinase Activation in Monocytes Is Independent of Ras J. Biol. Chem., October 16, 1998; 273(42): 27610 - 27619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ziogas, I. C. Lorenz, K. Moelling, and G. Radziwill Mitotic Raf-1 Is Stimulated Independently of Ras and Is Active in the Cytoplasm J. Biol. Chem., September 11, 1998; 273(37): 24108 - 24114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Winkler, R. E. Cutler Jr., J. K. Drugan, S. Campbell, D. K. Morrison, and J. A. Cooper Identification of Residues in the Cysteine-rich Domain of Raf-1 That Control Ras Binding and Raf-1 Activity J. Biol. Chem., August 21, 1998; 273(34): 21578 - 21584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Vojtek and C. J. Der Increasing Complexity of the Ras Signaling Pathway J. Biol. Chem., August 7, 1998; 273(32): 19925 - 19928. [Full Text] [PDF]
|
|
|
|
|
|
R. E. Cutler Jr., R. M. Stephens, M. R. Saracino, and D. K. Morrison Autoregulation of the Raf-1 serine/threonine kinase PNAS, August 4, 1998; 95(16): 9214 - 9219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Roy, R. A. McPherson, A. Apolloni, J. Yan, A. Lane, J. Clyde-Smith, and J. F. Hancock 14-3-3 Facilitates Ras-Dependent Raf-1 Activation In Vitro and In Vivo Mol. Cell. Biol., July 1, 1998; 18(7): 3947 - 3955. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. E. Aplin, A. Howe, S. K. Alahari, and R. L. Juliano Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins Pharmacol. Rev., June 1, 1998; 50(2): 197 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ohnishi, Y. Yamawaki-Kataoka, K.-i. Kariya, M. Tamada, C.-D. Hu, and T. Kataoka Selective Inhibition of Ras Interaction with Its Particular Effector by Synthetic Peptides Corresponding to the Ras Effector Region J. Biol. Chem., April 24, 1998; 273(17): 10210 - 10215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shirouzu, K. Morinaka, S. Koyama, C.-D. Hu, N. Hori-Tamura, T. Okada, K.-i. Kariya, T. Kataoka, A. Kikuchi, and S. Yokoyama Interactions of the Amino Acid Residue at Position 31 of the c-Ha-Ras Protein with Raf-1 and RalGDS J. Biol. Chem., March 27, 1998; 273(13): 7737 - 7742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Jaitner, J. Becker, T. Linnemann, C. Herrmann, A. Wittinghofer, and C. Block Discrimination of Amino Acids Mediating Ras Binding from Noninteracting Residues Affecting Raf Activation by Double Mutant Analysis J. Biol. Chem., November 21, 1997; 272(47): 29927 - 29933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Clark, J. K. Drugan, K. L. Rossman, J. W. Carpenter, K. Rogers-Graham, H. Fu, C. J. Der, and S. L. Campbell 14-3-3 zeta Negatively Regulates Raf-1 Activity by Interactions with the Raf-1 Cysteine-rich Domain J. Biol. Chem., August 22, 1997; 272(34): 20990 - 20993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Roy, A. Lane, J. Yan, R. McPherson, and J. F. Hancock Activity of Plasma Membrane-recruited Raf-1 Is Regulated by Ras via the Raf Zinc Finger J. Biol. Chem., August 8, 1997; 272(32): 20139 - 20145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Han, D. Wong, A. Dhaka, D. Afar, M. White, W. Xie, H. Herschman, O. Witte, and J. Colicelli Protein binding and signaling properties of RIN1 suggest a unique effector function PNAS, May 13, 1997; 94(10): 4954 - 4959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-D. Hu, K.-i. Kariya, G. Kotani, M. Shirouzu, S. Yokoyama, and T. Kataoka Coassociation of Rap1A and Ha-Ras with Raf-1 N-terminal Region Interferes with Ras-dependent Activation of Raf-1 J. Biol. Chem., May 2, 1997; 272(18): 11702 - 11705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mineo, R. G.W. Anderson, and M. A. White Physical Association with Ras Enhances Activation of Membrane-bound Raf (RafCAAX) J. Biol. Chem., April 18, 1997; 272(16): 10345 - 10348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Clark, M. S. Kinch, K. Rogers-Graham, S. M. Sebti, A. D. Hamilton, and C. J. Der The Ras-related Protein Rheb Is Farnesylated and Antagonizes Ras Signaling and Transformation J. Biol. Chem., April 18, 1997; 272(16): 10608 - 10615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Clark, J. K. Westwick, and C. J. Der p120 GAP Modulates Ras Activation of Jun Kinases and Transformation J. Biol. Chem., January 17, 1997; 272(3): 1677 - 1681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Sung, M.-C. C. Hwang, and Y.-W. Hwang The Dominant Negative Effects of H-Ras Harboring a Gly to Ala Mutation at Position 60 J. Biol. Chem., November 29, 1996; 271(48): 30537 - 30543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
ScottN. Peterson, L. Trabalzini, TeresaR. Brtva, T. Fischer, DanielL. Altschuler, P. Martelli, EduardoG. Lapetina, ChanningJ. Der, and GilbertC. White II Identification of a Novel RalGDS-related Protein as a Candidate Effector for Ras and Rap1 J. Biol. Chem., November 22, 1996; 271(47): 29903 - 29908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. P. Whitehead, R. Khosravi-Far, H. Kirk, G. Trigo-Gonzalez, C. J. Der, and R. Kay Expression Cloning of lsc, a Novel Oncogene with Structural Similarities to the Dbl Family of Guanine Nucleotide Exchange Factors J. Biol. Chem., August 2, 1996; 271(31): 18643 - 18650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Chen, T. H. Lin, C. J. Der, and R. L. Juliano Integrin-mediated Activation of MEK and Mitogen-activated Protein Kinase Is Independent of Ras J. Biol. Chem., July 26, 1996; 271(30): 18122 - 18127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mineo, G. L. James, E. J. Smart, and R. G. W. Anderson Localization of Epidermal Growth Factor-stimulated Ras/Raf-1 Interaction to Caveolae Membrane J. Biol. Chem., May 17, 1996; 271(20): 11930 - 11935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hiwasa, T. Sawada, and S. Sakiyama Synergistic Induction of Anchorage-independent Growth of NIH3T3 Mouse Fibroblasts by Cysteine Proteinase Inhibitors and a Tumor Promoter J. Biol. Chem., April 19, 1996; 271(16): 9181 - 9184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Galang, J. J. García-Ramírez, P. A. Solski, J. K. Westwick, C. J. Der, N. N. Neznanov, R. G. Oshima, and C. A. Hauser Oncogenic Neu/ErbB-2 Increases Ets, AP-1, and NF-kappaB-dependent Gene Expression, and Inhibiting Ets Activation Blocks Neu-mediated Cellular Transformation J. Biol. Chem., April 5, 1996; 271(14): 7992 - 7998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-C. C. Hwang, Y.-J. Sung, and Y.-W. Hwang The Differential Effects of the Gly-60 to Ala Mutation on the Interaction of H-Ras p21 with Different Downstream Targets J. Biol. Chem., April 5, 1996; 271(14): 8196 - 8202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gorman, R. H. Skinner, J. V. Skelly, S. Neidle, and P. N. Lowe Equilibrium and Kinetic Measurements Reveal Rapidly Reversible Binding of Ras to Raf J. Biol. Chem., March 22, 1996; 271(12): 6713 - 6719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Akasaka, M. Tamada, F. Wang, K.-i. Kariya, F. Shima, A. Kikuchi, M. Yamamoto, M. Shirouzu, S. Yokoyama, and T. Kataoka Differential Structural Requirements for Interaction of Ras Protein with Its Distinct Downstream Effectors J. Biol. Chem., March 8, 1996; 271(10): 5353 - 5360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Williams, J. K. Drugan, G.-S. Yi, G. J. Clark, C. J. Der, and S. L. Campbell Elucidation of Binding Determinants and Functional Consequences of Ras/Raf-Cysteine-rich Domain Interactions J. Biol. Chem., July 14, 2000; 275(29): 22172 - 22179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Booden, D. S. Sakaguchi, and J. E. Buss Mutation of Ha-Ras C Terminus Changes Effector Pathway Utilization J. Biol. Chem., July 28, 2000; 275(31): 23559 - 23568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kim, M.-Y. Yoon, S.-L. Choi, I. Kang, S.-S. Kim, Y.-S. Kim, Y.-K. Choi, and J. Ha Effects of Stimulation of AMP-activated Protein Kinase on Insulin-like Growth Factor 1- and Epidermal Growth Factor-dependent Extracellular Signal-regulated Kinase Pathway J. Biol. Chem., May 25, 2001; 276(22): 19102 - 19110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Luttrell, F. L. Roudabush, E. W. Choy, W. E. Miller, M. E. Field, K. L. Pierce, and R. J. Lefkowitz Activation and targeting of extracellular signal-regulated kinases by beta -arrestin scaffolds PNAS, February 27, 2001; 98(5): 2449 - 2454. [Abstract] [Full Text] [ |
