JBC INTERFERin siRNA transfection reagent

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Winkler, D. G.
Right arrow Articles by Cooper, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Winkler, D. G.
Right arrow Articles by Cooper, J. A.

J Biol Chem, Vol. 273, Issue 34, 21578-21584, August 21, 1998

Identification of Residues in the Cysteine-rich Domain of Raf-1 That Control Ras Binding and Raf-1 Activity

David G. WinklerDagger , Richard E. Cutler Jr., Jonelle K. DruganDagger Dagger , Sharon CampbellDagger Dagger , Deborah K. Morrison, and Jonathan A. CooperDagger

From the Dagger  Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, the  Molecular Basis of Carcinogenesis Laboratory, ABL-Basic Research, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, and the Dagger Dagger  Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599

We have identified mutations in Raf-1 that increase binding to Ras. The mutations were identified making use of three mutant forms of Ras that have reduced Raf-1 binding (Winkler, D. G., Johnson, J. C., Cooper, J. A., and Vojtek, A. B. (1997) J. Biol. Chem. 272, 24402-24409). One mutation in Raf-1, N64L, suppresses the Ras mutant R41Q but not other Ras mutants, suggesting that this mutation structurally complements the Ras R41Q mutation. Missense substitutions of residues 143 and 144 in the Raf-1 cysteine-rich domain were isolated multiple times. These Raf-1 mutants, R143Q, R143W, and K144E, were general suppressors of three different Ras mutants and had increased interaction with non-mutant Ras. Each was slightly activated relative to wild-type Raf-1 in a transformation assay. In addition, two mutants, R143W and K144E, were active when tested for induction of germinal vesicle breakdown in Xenopus oocytes. Interestingly, all three cysteine-rich domain mutations reduced the ability of the Raf-1 N-terminal regulatory region to inhibit Xenopus oocyte germinal vesicle breakdown induced by the C-terminal catalytic region of Raf-1. We propose that a direct or indirect regulatory interaction between the N- and C-terminal regions of Raf-1 is reduced by the R143W, R143Q, and K144E mutations, thereby increasing access to the Ras-binding regions of Raf-1 and increasing Raf-1 activity.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
S. Sato, N. Fujita, and T. Tsuruo
Involvement of 3-Phosphoinositide-dependent Protein Kinase-1 in the MEK/MAPK Signal Transduction Pathway
J. Biol. Chem., August 6, 2004; 279(32): 33759 - 33767.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
S. Carrasco and I. Merida
Diacylglycerol-dependent Binding Recruits PKC{theta} and RasGRP1 C1 Domains to Specific Subcellular Localizations in Living T Lymphocytes
Mol. Biol. Cell, June 1, 2004; 15(6): 2932 - 2942.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Zang, C. Hayne, and Z. Luo
Interaction between Active Pak1 and Raf-1 Is Necessary for Phosphorylation and Activation of Raf-1
J. Biol. Chem., February 1, 2002; 277(6): 4395 - 4405.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Nantel, M. Huber, and D. Y. Thomas
Localization of Endogenous Grb10 to the Mitochondria and Its Interaction with the Mitochondrial-associated Raf-1 Pool
J. Biol. Chem., December 10, 1999; 274(50): 35719 - 35724.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 J. Biol. Chem.Home page
H.-Y. Kim, M. Akbar, A. Lau, and L. Edsall
Inhibition of Neuronal Apoptosis by Docosahexaenoic Acid (22:6n-3). ROLE OF PHOSPHATIDYLSERINE IN ANTIAPOPTOTIC EFFECT
J. Biol. Chem., November 3, 2000; 275(45): 35215 - 35223.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. R. Xing and R. Kolesnick
Kinase Suppressor of Ras Signals through Thr269 of c-Raf-1
J. Biol. Chem., March 23, 2001; 276(13): 9733 - 9741.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Zang, C. A. Waelde, X. Xiang, A. Rana, R. Wen, and Z. Luo
Microtubule Integrity Regulates Pak Leading to Ras-independent Activation of Raf-1. INSIGHTS INTO MECHANISMS OF Raf-1 ACTIVATION
J. Biol. Chem., June 29, 2001; 276(27): 25157 - 25165.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.