| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 5, 3691-3695, February 2, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Mutations in the epidermal growth
factor receptor have been identified in several human tumor
types, including gliomas. These receptor mutants have deletions in
their extracellular ligand-binding domains and are, therefore, no
longer regulated by ligand, resulting in constitutive activation of the
receptor kinase. These mutants have been proposed to transduce
oncogenic signals via ligand-independent signaling pathways. Avian
viral homologues of these oncogenic epidermal growth factor receptors
exhibit structurally homologous deletions and form tumors in chickens.
One such mutant, S3v-ErbB, transforms fibroblasts in vitro,
and transformation has been correlated with the formation of a novel
tyrosine phosphoprotein complex. V-ErbB-mediated complex formation and
transformation have been shown to occur independently of Ras
activation. The major aims of this study are to further characterize
this ligand-independent v-ErbB oncogenic signaling pathway. Here we
show that both v-ErbB-mediated phosphoprotein complex formation and
transformation are inhibited by a dominant negative mutant of Rho. This
inhibition is specific for dominant negative Rho; dominant negative
mutants of Rac and Cdc42 have no effect on transformation or on
tyrosine phosphorylation of the phosphoprotein complex. Based on these
observations, we propose that S3v-ErbB stimulates a
Rho-dependent tyrosine kinase, resulting in complex
formation and ultimately oncogenic transformation.
Activation of Rho Is Required for Ligand-independent Oncogenic
Signaling by a Mutant Epidermal Growth Factor Receptor*
§,
, and**
Tumor Biology Program, Department of
Biochemistry, and ¶ Department of Pediatrics, Mayo Clinic,
Rochester, Minnesota 55905
*
This work was supported by National Institutes of Health
Grants CA75238 (to M. J. M.) and CA 79808 (to N. J. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Current address: Dept. of Molecular and Experimental Medicine,
Scripps Research Inst., La Jolla, CA 92037.
**
To whom correspondence should be addressed: Mayo Clinic, 200 1st
St. SW, Rochester, MN 55905. Tel.: 507-284-8121; E-mail: Maihle@mayo.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Q. Chang and G. D. Fischbach An Acute Effect of Neuregulin 1beta to Suppress {alpha}7-Containing Nicotinic Acetylcholine Receptors in Hippocampal Interneurons. J. Neurosci., November 1, 2006; 26(44): 11295 - 11303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Boerner, M. L. Demory, C. Silva, and S. J. Parsons Phosphorylation of Y845 on the Epidermal Growth Factor Receptor Mediates Binding to the Mitochondrial Protein Cytochrome c Oxidase Subunit II Mol. Cell. Biol., August 15, 2004; 24(16): 7059 - 7071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Learn, T. L. Hartzell, C. J. Wikstrand, G. E. Archer, J. N. Rich, A. H. Friedman, H. S. Friedman, D. D. Bigner, and J. H. Sampson Resistance to Tyrosine Kinase Inhibition by Mutant Epidermal Growth Factor Receptor Variant III Contributes to the Neoplastic Phenotype of Glioblastoma Multiforme Clin. Cancer Res., May 1, 2004; 10(9): 3216 - 3224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsutsumi, T. Taketani, K. Nishimura, X. Ge, T. Taki, K. Sugita, E. Ishii, R. Hanada, M. Ohki, H. Aburatani, et al. Two Distinct Gene Expression Signatures in Pediatric Acute Lymphoblastic Leukemia with MLL Rearrangements Cancer Res., August 15, 2003; 63(16): 4882 - 4887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Wolf, N. Draghi, X. Liang, C. Dai, L. Uhrbom, C. Eklof, B. Westermark, E. C. Holland, and M. D. Resh p190RhoGAP can act to inhibit PDGF-induced gliomas in mice: a putative tumor suppressor encoded on human Chromosome 19q13.3 Genes & Dev., February 15, 2003; 17(4): 476 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen and M. D. Resh Cholesterol Depletion from the Plasma Membrane Triggers Ligand-independent Activation of the Epidermal Growth Factor Receptor J. Biol. Chem., December 13, 2002; 277(51): 49631 - 49637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Renkema, K. Pulkkinen, and K. Saksela Cdc42/Rac1-Mediated Activation Primes PAK2 for Superactivation by Tyrosine Phosphorylation Mol. Cell. Biol., October 1, 2002; 22(19): 6719 - 6725. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Nguyen, C. S. Zong, S. Uttamsingh, P. Sachdev, M. Bhanot, M.-T. Le, J. L.-K. Chan, and L.-H. Wang The Role of Phosphatidylinositol 3-Kinase, Rho Family GTPases, and STAT3 in Ros-induced Cell Transformation J. Biol. Chem., March 22, 2002; 277(13): 11107 - 11115. [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 |
