JBC Avanti Polar Lipids

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


     

Originally published In Press as doi:10.1074/jbc.M102803200 on May 22, 2001

J. Biol. Chem., Vol. 276, Issue 30, 27793-27798, July 27, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/30/27793    most recent
M102803200v1
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 Zhou, J.
Right arrow Articles by Hsieh, J.-T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, J.
Right arrow Articles by Hsieh, J.-T.
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?

The Inhibitory Role of DOC-2/DAB2 in Growth Factor Receptor-mediated Signal Cascade
DOC-2/DAB2-MEDIATED INHIBITION OF ERK PHOSPHORYLATION VIA BINDING TO Grb2*

Jian Zhou and Jer-Tsong HsiehDagger

From the Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110

DOC-2/DAB2 (differentially expressed in ovarian carcinoma-2/disabled 2) appears to be a potential tumor suppressor gene with a growth inhibitory effect on several cancer types. Previously, we have shown that DOC-2/DAB2 suppresses protein kinase C-induced AP-1 activation, which is modulated by serine 24 phosphorylation in the N terminus of DOC-2/DAB2. However, the functional impact of the C terminus of DOC-2/DAB2, containing three proline-rich domains, has not been explored. In this study, we examined this functional role in modulating signaling mediated by peptide growth factor receptor tyrosine kinase, particularly because it involves the interaction with Grb2. Using sequence-specific peptides, we found that the second proline-rich domain of DOC-2/DAB2 is the key binding site to Grb2 in the presence of growth factors. Such elevated binding interrupts the binding between SOS and Grb2, which consequently suppresses downstream ERK phosphorylation. Reduced ERK phosphorylation was restored when the binding between DOC-2/DAB2 and Grb2 was interrupted by a specific peptide or by increasing the expression of Grb2. Furthermore, the C terminus of the DOC-2/DAB2 construct can inhibit the AP-1 activity elicited by growth factors. We conclude that DOC-2/DAB2, a potent negative regulator, can suppress ERK activation by interrupting the binding between Grb2 and SOS that is elicited by peptide growth factors. This study further illustrates that DOC-2/DAB2 has multiple effects on the RAS-mediated signal cascades active in cancer cells.

* This work was supported in part by National Institutes of Health Grant CA 59939, by United States Army Grant PC970259, and by funds from the Gillson Longenbaugh Foundation.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.

Dagger To whom correspondence should be addressed: University of Texas Southwestern Medical Center, Dept. of Urology, 5323 Harry Hines Blvd., Dallas, TX 75390-9110. Tel.: 214-648-3988; Fax: 214-648-8786; E-mail: JT.Hsieh@UTSouthwestern.edu.

Copyright © 2001 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
A. Fadloun, D. Kobi, J.-C. Pointud, A. K. Indra, M. Teletin, C. Bole-Feysot, B. Testoni, R. Mantovani, D. Metzger, G. Mengus, et al.
The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour suppressor activity in mouse epidermis
Development, August 15, 2007; 134(16): 2947 - 2958.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. A. Karam, S. F. Shariat, H.-Y. Huang, R.-C. Pong, R. Ashfaq, E. Shapiro, Y. Lotan, A. I. Sagalowsky, X.-R. Wu, and J.-T. Hsieh
Decreased DOC-2/DAB2 Expression in Urothelial Carcinoma of the Bladder
Clin. Cancer Res., August 1, 2007; 13(15): 4400 - 4406.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. G. Romero, L. L. Yanes, A. F. de Rodriguez, M. W. Plonczynski, B. L. Welsh, J. F. Reckelhoff, E. P. Gomez-Sanchez, and C. E. Gomez-Sanchez
Disabled-2 Is Expressed in Adrenal Zona Glomerulosa and Is Involved in Aldosterone Secretion
Endocrinology, June 1, 2007; 148(6): 2644 - 2652.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
D. H. Kumbar, A. VanBergen, C. Ocampo, S. Muangmingsuk, A. J. Griffin, and M. Gupta
Adapter molecule DOC-2 is differentially expressed in pressure and volume overload hypertrophy and inhibits collagen synthesis in cardiac fibroblasts
J Appl Physiol, May 1, 2007; 102(5): 2024 - 2032.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I. Tossidou, C. Kardinal, I. Peters, W. Kriz, A. Shaw, I. Dikic, S. Tkachuk, I. Dumler, H. Haller, and M. Schiffer
CD2AP/CIN85 Balance Determines Receptor Tyrosine Kinase Signaling Response in Podocytes
J. Biol. Chem., March 9, 2007; 282(10): 7457 - 7464.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Zhou, J. Fan, and J.-T. Hsieh
Inhibition of Mitogen-Elicited Signal Transduction and Growth in Prostate Cancer with a Small Peptide Derived from the Functional Domain of DOC-2/DAB2 Delivered by a Unique Vehicle.
Cancer Res., September 15, 2006; 66(18): 8954 - 8958.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D.-H. Yang, Z. Fazili, E. R. Smith, K. Q. Cai, A. Klein-Szanto, C. Cohen, I. R. Horowitz, and X.-X. Xu
Disabled-2 Heterozygous Mice Are Predisposed to Endometrial and Ovarian Tumorigenesis and Exhibit Sex-Biased Embryonic Lethality in a p53-Null Background
Am. J. Pathol., July 1, 2006; 169(1): 258 - 267.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Zhoul, G. Hernandez, S.-W. Tu, C.-L. Huang, C.-P. Tseng, and J.-T. Hsieh
The Role of DOC-2/DAB2 in Modulating Androgen Receptor-Mediated Cell Growth via the Nongenomic c-Src-Mediated Pathway in Normal Prostatic Epithelium and Cancer
Cancer Res., November 1, 2005; 65(21): 9906 - 9913.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Zhou, G. Hernandez, S.-w. Tu, J. Scholes, H. Chen, C.-P. Tseng, and J.-T. Hsieh
Synergistic Induction of DOC-2/DAB2 Gene Expression in Transitional Cell Carcinoma in the Presence of GATA6 and Histone Deacetylase Inhibitor
Cancer Res., July 15, 2005; 65(14): 6089 - 6096.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Prunier and P. H. Howe
Disabled-2 (Dab2) Is Required for Transforming Growth Factor {beta}-induced Epithelial to Mesenchymal Transition (EMT)
J. Biol. Chem., April 29, 2005; 280(17): 17540 - 17548.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C.-L. Huang, J.-C. Cheng, C.-H. Liao, A. Stern, J.-T. Hsieh, C.-H. Wang, H.-L. Hsu, and C.-P. Tseng
Disabled-2 Is a Negative Regulator of Integrin {alpha}IIb{beta}3-mediated Fibrinogen Adhesion and Cell Signaling
J. Biol. Chem., October 1, 2004; 279(40): 42279 - 42289.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Fernandez-Madrid, N. Tang, H. Alansari, J. L. Granda, L. Tait, K. C. Amirikia, M. Moroianu, X. Wang, and R. L. Karvonen
Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer
Cancer Res., August 1, 2004; 64(15): 5089 - 5096.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
H. Dote, S. Toyooka, K. Tsukuda, M. Yano, M. Ouchida, H. Doihara, M. Suzuki, H. Chen, J.-T. Hsieh, A. F. Gazdar, et al.
Aberrant Promoter Methylation in Human DAB2 Interactive Protein (hDAB2IP) Gene in Breast Cancer
Clin. Cancer Res., March 15, 2004; 10(6): 2082 - 2089.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Zhou, J. Scholes, and J.-T. Hsieh
Characterization of a Novel Negative Regulator (DOC-2/DAB2) of c-Src in Normal Prostatic Epithelium and Cancer
J. Biol. Chem., February 21, 2003; 278(9): 6936 - 6941.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Chen, S. Toyooka, A. F. Gazdar, and J.-T. Hsieh
Epigenetic Regulation of a Novel Tumor Suppressor Gene (hDAB2IP) in Prostate Cancer Cell Lines
J. Biol. Chem., January 24, 2003; 278(5): 3121 - 3130.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. M. J. van der Meijden, D. S. Lapointe, M. X. Luong, D. Peric-Hupkes, B. Cho, J. L. Stein, A. J. van Wijnen, and G. S. Stein
Gene Profiling of Cell Cycle Progression through S-Phase Reveals Sequential Expression of Genes Required for DNA Replication and Nucleosome Assembly
Cancer Res., June 1, 2002; 62(11): 3233 - 3243.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
C. E. Rocheleau, R. M. Howard, A. P. Goldman, M. L. Volk, L. J. Girard, and M. V. Sundaram
A lin-45 raf Enhancer Screen Identifies eor-1, eor-2 and Unusual Alleles of Ras Pathway Genes in Caenorhabditis elegans
Genetics, May 1, 2002; 161(1): 121 - 131.
[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 © 2001 by the American Society for Biochemistry and Molecular Biology.