JBC

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 Li, J.
Right arrow Articles by Smithgall, T. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, J.
Right arrow Articles by Smithgall, T. 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?

J Biol Chem, Vol. 273, Issue 22, 13828-13834, May 29, 1998

Fibroblast Transformation by Fps/Fes Tyrosine Kinases Requires Ras, Rac, and Cdc42 and Induces Extracellular Signal-regulated and c-Jun N-terminal Kinase Activation

Jianze Li and Thomas E. Smithgall

From the Eppley Institute for Research in Cancer and Department of Pharmacology University of Nebraska Medical Center, Omaha, Nebraska 68198-6805

The small GTP-binding proteins Ras, Rac, and Cdc42 link protein-tyrosine kinases with mitogen-activated protein kinase (MAPK) signaling cascades. Ras controls the activation of extracellular signal-regulated kinases (ERKs), while Rac and Cdc42 regulate the c-Jun N-terminal kinases (JNKs). In this study, we investigated whether small G protein/MAPK cascades contribute to signal transduction by transforming variants of c-Fes, a nonreceptor tyrosine kinase implicated in cytokine signaling and myeloid differentiation. First, we investigated the effects of dominant-negative small G proteins on Rat-2 fibroblast transformation by a retroviral homolog of c-Fes (v-Fps) and by c-Fes activated via N-terminal addition of the v-Src myristylation signal (Myr-Fes). We observed that dominant-negative Ras, Rac, and Cdc42 inhibited v-Fps- and Myr-Fes-induced growth of Rat-2 cells in soft agar, indicating that activation of these small GTP-binding proteins is required for fibroblast transformation by Fps/Fes tyrosine kinases. To determine whether MAPK pathways are activated downstream of these small G proteins, we measured ERK and JNK activity in the v-Fps- and Myr-Fes-transformed Rat-2 cells. Both ERK and JNK activities were elevated in the transformed cells, suggesting that these pathways are involved in cellular transformation. Dominant-negative mutants of Ras (but not Rac or Cdc42) specifically inhibited ERK activation by v-Fps and Myr-Fes, demonstrating that ERK activation occurs exclusively downstream of Ras. All three dominant-negative small G proteins inhibited JNK activation by v-Fps and Myr-Fes, indicating that JNK activation by these tyrosine kinases requires both Ras and Rho family GTPases. These data demonstrate that multiple small G protein/MAPK cascades are involved in downstream signal transduction by Fps/Fes tyrosine kinases.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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
 DevelopmentHome page
M. J. Murray, C. M. Davidson, N. M. Hayward, and A. H. Brand
The Fes/Fer non-receptor tyrosine kinase cooperates with Src42A to regulate dorsal closure in Drosophila
Development, August 15, 2006; 133(16): 3063 - 3073.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Y. F. Kam, A. S. L. Chan, and Y. H. Wong
{kappa}-Opioid Receptor Signals through Src and Focal Adhesion Kinase to Stimulate c-Jun N-Terminal Kinases in Transfected COS-7 Cells and Human Monocytic THP-1 Cells
J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 301 - 310.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. J. Haigh, M. Ema, K. Haigh, M. Gertsenstein, P. Greer, J. Rossant, A. Nagy, and E. F. Wagner
Activated Fps/Fes partially rescues the in vivo developmental potential of Flk1-deficient vascular progenitor cells
Blood, February 1, 2004; 103(3): 912 - 920.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
R. A. Zirngibl, Y. Senis, and P. A. Greer
Enhanced Endotoxin Sensitivity in Fps/Fes-Null Mice with Minimal Defects in Hematopoietic Homeostasis
Mol. Cell. Biol., April 15, 2002; 22(8): 2472 - 2486.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Y. Cheng, A. P. Schiavone, and T. E. Smithgall
A Point Mutation in the N-Terminal Coiled-Coil Domain Releases c-Fes Tyrosine Kinase Activity and Survival Signaling in Myeloid Leukemia Cells
Mol. Cell. Biol., September 15, 2001; 21(18): 6170 - 6180.
[Abstract] [Full Text] [PDF]

Home page
 Cell Growth Differ.Home page
J. A. Rogers, H. Y. Cheng, and T. E. Smithgall
Src Homology 2 Domain Substitution Modulates the Kinase and Transforming Activities of the Fes Protein-Tyrosine Kinase
Cell Growth Differ., November 1, 2000; 11(11): 581 - 592.
[Abstract] [Full Text]

Home page
 BloodHome page
E. Rovida, F. Marra, M. Baccarini, and P. D. Sbarba
Constitutive activation of the MAPK pathway mediates v-fes-induced mitogenesis in murine macrophages
Blood, June 15, 2000; 95(12): 3959 - 3963.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Kanda, E. C. Lerner, S. Tsuda, T. Shono, H. Kanetake, and T. E. Smithgall
The Nonreceptor Protein-tyrosine Kinase c-Fes Is Involved in Fibroblast Growth Factor-2-induced Chemotaxis of Murine Brain Capillary Endothelial Cells
J. Biol. Chem., March 31, 2000; 275(14): 10105 - 10111.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. M. Lionberger and T. E. Smithgall
The c-Fes Protein-Tyrosine Kinase Suppresses Cytokine-independent Outgrowth of Myeloid Leukemia Cells Induced by Bcr-Abl
Cancer Res., February 1, 2000; 60(4): 1097 - 1103.
[Abstract] [Full Text]

Home page
 Mol. Cell. Biol.Home page
H. Cheng, J. A. Rogers, N. A. Dunham, and T. E. Smithgall
Regulation of c-Fes Tyrosine Kinase and Biological Activities by N-Terminal Coiled-Coil Oligomerization Domains
Mol. Cell. Biol., December 1, 1999; 19(12): 8335 - 8343.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. Turkson, T. Bowman, J. Adnane, Y. Zhang, J. Y. Djeu, M. Sekharam, D. A. Frank, L. B. Holzman, J. Wu, S. Sebti, et al.
Requirement for Ras/Rac1-Mediated p38 and c-Jun N-Terminal Kinase Signaling in Stat3 Transcriptional Activity Induced by the Src Oncoprotein
Mol. Cell. Biol., November 1, 1999; 19(11): 7519 - 7528.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
D. I. Johnson
Cdc42: An Essential Rho-Type GTPase Controlling Eukaryotic Cell Polarity
Microbiol. Mol. Biol. Rev., March 1, 1999; 63(1): 54 - 105.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. M. Lionberger, M. B. Wilson, and T. E. Smithgall
Transformation of Myeloid Leukemia Cells to Cytokine Independence by Bcr-Abl Is Suppressed by Kinase-defective Hck
J. Biol. Chem., June 9, 2000; 275(24): 18581 - 18585.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. D. Briggs, B. Scholtz, J.-M. Jacque, S. Swingler, M. Stevenson, and T. E. Smithgall
HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway
J. Biol. Chem., June 29, 2001; 276(27): 25605 - 25611.
[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.