JBC Oz Biosciences

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


     


Originally published In Press as doi:10.1074/jbc.M406395200 on September 13, 2004

J. Biol. Chem., Vol. 279, Issue 46, 47808-47814, November 12, 2004
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
279/46/47808    most recent
M406395200v1
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 Razidlo, G. L.
Right arrow Articles by Lewis, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Razidlo, G. L.
Right arrow Articles by Lewis, R. E.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Phosphorylation Regulates KSR1 Stability, ERK Activation, and Cell Proliferation*{boxs}

Gina L. Razidlo{ddagger}§, Robert L. Kortum{ddagger}§, Jamie L. Haferbier{ddagger}, and Robert E. Lewis{ddagger}§||

From the {ddagger}Eppley Institute for Research in Cancer and Allied Diseases and the §Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-7696

Kinase suppressor of Ras (KSR) is a molecular scaffold that interacts with the components of the Raf/MEK/ERK kinase cascade and positively regulates ERK signaling. Phosphorylation of KSR1, particularly at Ser392, is a critical regulator of KSR1 subcellular localization and ERK activation. We examined the role of phosphorylation of both Ser392 and Thr274 in regulating ERK activation and cell proliferation. We hypothesized that KSR1 phosphorylation is involved in generating signaling specificity through the Raf/MEK/ERK kinase cascade in response to stimulation by different growth factors. In fibroblasts, platelet-derived growth factor stimulation induces sustained ERK activation and promotes S-phase entry. Treatment with epidermal growth factor induces transient ERK activation but fails to drive cells into S phase. Mutation of Ser392 and Thr274 (KSR1.TVSA) promotes sustained ERK activation and cell cycle progression with either platelet-derived growth factor or epidermal growth factor treatment. KSR1–/– mouse embryo fibroblasts expressing KSR1.TVSA proliferate two times faster and grow to a higher density than cells expressing the same level of wild-type KSR1. In addition, KSR1.TVSA is more stable than wild-type KSR1. These data demonstrate that phosphorylation and stability of the molecular scaffold KSR1 are critical regulators of growth factor-specific responses that promote cell proliferation.


Received for publication, June 8, 2004 , and in revised form, August 24, 2004.

* This research was supported by National Institutes of Health Grants CA90400 and CA36727. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains a supplementary figure showing fluorescent photomicrographs of anti-BrdUrd- and 4',6-diamidino-2-phenylindole-stained cells.

Supported by a predoctoral fellowship from the National Science Foundation.

|| To whom correspondence should be addressed: Eppley Institute, University of Nebraska Medical Center, 987696 Nebraska Medical Center, Omaha, NE 68198-7696. Tel.: 402-559-8290; Fax: 402-559-3739; E-mail: rlewis{at}unmc.edu.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
Mol. Endocrinol.Home page
E. M. Horvath, L. Tackett, A. M. McCarthy, P. Raman, J. T. Brozinick, and J. S. Elmendorf
Antidiabetogenic Effects of Chromium Mitigate Hyperinsulinemia-Induced Cellular Insulin Resistance via Correction of Plasma Membrane Cholesterol Imbalance
Mol. Endocrinol., April 1, 2008; 22(4): 937 - 950.
[Abstract] [Full Text] [PDF]


Home page
J Biomol ScreenHome page
J. Szwaya, C. Bruseo, E. Nakuci, D. McSweeney, X. Xiang, D. Senator, D. France, and C.-R. Chen
A Novel Platform for Accelerated Pharmacodynamic Profiling for Lead Optimization of Anticancer Drug Candidates
J Biomol Screen, March 1, 2007; 12(2): 159 - 166.
[Abstract] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
A. M. McCarthy, K. O. Spisak, J. T. Brozinick, and J. S. Elmendorf
Loss of cortical actin filaments in insulin-resistant skeletal muscle cells impairs GLUT4 vesicle trafficking and glucose transport
Am J Physiol Cell Physiol, November 1, 2006; 291(5): C860 - C868.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
R. L. Kortum, H. J. Johnson, D. L. Costanzo, D. J. Volle, G. L. Razidlo, A. M. Fusello, A. S. Shaw, and R. E. Lewis
The Molecular Scaffold Kinase Suppressor of Ras 1 Is a Modifier of RasV12-Induced and Replicative Senescence.
Mol. Cell. Biol., March 1, 2006; 26(6): 2202 - 2214.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
L. K. Rushworth, A. D. Hindley, E. O'Neill, and W. Kolch
Regulation and role of raf-1/b-raf heterodimerization.
Mol. Cell. Biol., March 1, 2006; 26(6): 2262 - 2272.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
S. E. Robertson, S. R. G. Setty, A. Sitaram, M. S. Marks, R. E. Lewis, and M. M. Chou
Extracellular Signal-regulated Kinase Regulates Clathrin-independent Endosomal Trafficking
Mol. Biol. Cell, February 1, 2006; 17(2): 645 - 657.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
R. L. Kortum, D. L. Costanzo, J. Haferbier, S. J. Schreiner, G. L. Razidlo, M.-H. Wu, D. J. Volle, T. Mori, H. Sakaue, N. V. Chaika, et al.
The Molecular Scaffold Kinase Suppressor of Ras 1 (KSR1) Regulates Adipogenesis
Mol. Cell. Biol., September 1, 2005; 25(17): 7592 - 7604.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
A. B. Strawbridge and J. S. Elmendorf
Phosphatidylinositol 4,5-Bisphosphate Reverses Endothelin-1-Induced Insulin Resistance via an Actin-Dependent Mechanism
Diabetes, June 1, 2005; 54(6): 1698 - 1705.
[Abstract] [Full Text] [PDF]


Home page
Sci SignalHome page
A. Laine and Z. Ronai
Ubiquitin Chains in the Ladder of MAPK Signaling
Sci. Signal., April 26, 2005; 2005(281): re5 - re5.
[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 © 2004 by the American Society for Biochemistry and Molecular Biology.