JBC

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


     

Originally published In Press as doi:10.1074/jbc.M004302200 on July 20, 2000

J. Biol. Chem., Vol. 275, Issue 39, 30163-30168, September 29, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/39/30163    most recent
M004302200v1
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 Shangary, S.
Right arrow Articles by Baskaran, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shangary, S.
Right arrow Articles by Baskaran, R.
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?

Regulation of DNA-dependent Protein Kinase Activity by Ionizing Radiation-activated Abl Kinase Is an ATM-dependent Process*

Sanjeev ShangaryDagger , Kevin D. Brown§, Aaron W. Adamson§, Scott Edmonson||, Bobby NgDagger , Tej K. Pandita**Dagger Dagger , Jack Yalowich§§, Guillermo E. Taccioli||¶¶, and R. BaskaranDagger ||||

From the Dagger  Department of Molecular Genetics and Biochemistry and the §§ Department of Pharmacology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, the § Department of Biochemistry and Molecular Biology and the Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, the || Department of Microbiology, Boston University, School of Medicine, Boston, Massachusetts 02118, and the ** Center for Radiological Research, Columbia University, New York, New York 10032

Ionizing radiation (IR) treatment results in activation of the nonreceptor tyrosine kinase c-Abl because of phosphorylation by ATM. In vitro evidence indicates that DNA-dependent protein kinase (DNA-PK) can also phosphorylate and thus potentially activate Abl kinase activity in response to IR exposure. To unravel the role of ATM and DNA-PK in the activation of Abl, we assayed Abl, ATM, and DNA-PK activity in ATM- and DNA-PKcs-deficient cells after irradiation. Our results show that despite the presence of higher than normal levels of DNA-PK kinase activity, c-Abl fails to become activated after IR exposure in ATM-deficient cells. Conversely, normal activation of both ATM and c-Abl occurs in DNA-PKcs-deficient cells, indicating that ATM but not DNA-PK is required for activation of Abl in response to IR treatment. Moreover, activation of Abl kinase activity by IR correlates well with activation of ATM activity in all phases of the cell cycle. These results indicate that ATM is primarily responsible for activation of Abl in response to IR exposure in a cell cycle-independent fashion. Examination of DNA-PK activity in response to IR treatment in Abl-deficient cells expressing mutant forms of Abl or in normal cells exposed to an inhibitor of Abl suggests an in vivo role for Abl in the down-regulation of DNA-PK activity. Collectively, these results suggest a convergence of the ATM and DNA-PK pathways in the cellular response to IR through c-Abl kinase.

* This work was supported by Grant IRG-60-002-40 from the American Cancer Society (to R. B.).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.

Supported by American Cancer Society Grant GMC-98564.

Dagger Dagger Supported by National Institutes of Health Grant NS 34746.

¶¶ Supported by National Institutes of Health Grant CA76409 and American Cancer Society Grant IN97-T. Scholar of the Leukemia and Lymphoma Society.

|||| To whom correspondence should be addressed: Molecular Genetics and Biochemistry, E1205 Biomedical Science Tower, University of Pittsburgh Medical Center, Pittsburgh, PA 15261. Tel.: 412-648-9023; Fax: 412-624-1401; E-mail address: bask@pitt.edu.

Copyright © 2000 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
 J. Biol. Chem.Home page
W.-J. Kim, B. Rajasekaran, and K. D. Brown
MLH1- and ATM-dependent MAPK Signaling Is Activated through c-Abl in Response to the Alkylator N-Methyl-N'-nitro-N'-nitrosoguanidine
J. Biol. Chem., November 2, 2007; 282(44): 32021 - 32031.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
R. Kamath, Z. Jiang, G. Sun, J. C. Yalowich, and R. Baskaran
c-Abl Kinase Regulates Curcumin-Induced Cell Death through Activation of c-Jun N-Terminal Kinase
Mol. Pharmacol., January 1, 2007; 71(1): 61 - 72.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Li and D. F. Stern
Regulation of CHK2 by DNA-dependent Protein Kinase
J. Biol. Chem., March 25, 2005; 280(12): 12041 - 12050.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. G. Viniegra, N. Martinez, P. Modirassari, J. H. Losa, C. P. Cobo, V. J. S.-A. Lobo, C. I. A. Luquero, L. Alvarez-Vallina, S. Ramon y Cajal, J. M. Rojas, et al.
Full Activation of PKB/Akt in Response to Insulin or Ionizing Radiation Is Mediated through ATM
J. Biol. Chem., February 11, 2005; 280(6): 4029 - 4036.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. M. Vilenchik and A. G. Knudson
Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer
PNAS, October 28, 2003; 100(22): 12871 - 12876.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. Yang, Y. Yu, H. E. Hamrick, and P. J. Duerksen-Hughes
ATM, ATR and DNA-PK: initiators of the cellular genotoxic stress responses
Carcinogenesis, October 1, 2003; 24(10): 1571 - 1580.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Corde, J. Balosso, H. Elleaume, M. Renier, A. Joubert, M.-C. Biston, J.-F. Adam, A.-M. Charvet, T. Brochard, J.-F. Le Bas, et al.
Synchrotron Photoactivation of Cisplatin Elicits an Extra Number of DNA Breaks That Stimulate RAD51-mediated Repair Pathways
Cancer Res., June 15, 2003; 63(12): 3221 - 3227.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Lucero, D. Gae, and G. E. Taccioli
Novel Localization of the DNA-PK Complex in Lipid Rafts: A PUTATIVE ROLE IN THE SIGNAL TRANSDUCTION PATHWAY OF THE IONIZING RADIATION RESPONSE
J. Biol. Chem., June 6, 2003; 278(24): 22136 - 22143.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Bowen, M. Birrer, and E. P. Gelmann
Retinoblastoma Protein-mediated Apoptosis After gamma -Irradiation
J. Biol. Chem., November 15, 2002; 277(47): 44969 - 44979.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. W. Adamson, W.-J. Kim, S. Shangary, R. Baskaran, and K. D. Brown
ATM Is Activated in Response to N-Methyl-N'-nitro- N-nitrosoguanidine-induced DNA Alkylation
J. Biol. Chem., October 4, 2002; 277(41): 38222 - 38229.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. Cong, J. Tang, B. J. Hwang, B. Q. Vuong, G. Chu, and S. P. Goff
Interaction between UV-damaged DNA Binding Activity Proteins and the c-Abl Tyrosine Kinase
J. Biol. Chem., September 13, 2002; 277(38): 34870 - 34878.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. Wu, M.-b. Yin, G. Hapke, K. Toth, and Y. M. Rustum
Induction of Biphasic DNA Double Strand Breaks and Activation of Multiple Repair Protein Complexes by DNA Topoisomerase I Drug 7-Ethyl-10-hydroxy-camptothecin
Mol. Pharmacol., April 1, 2002; 61(4): 742 - 748.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Lan, Z. Sever-Chroneos, M. W. Strobeck, C.-H. Park, R. Baskaran, W. Edelmann, G. Leone, and E. S. Knudsen
DNA Damage Invokes Mismatch Repair-dependent Cyclin D1 Attenuation and Retinoblastoma Signaling Pathways to Inhibit CDK2
J. Biol. Chem., March 1, 2002; 277(10): 8372 - 8381.
[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 © 2000 by the American Society for Biochemistry and Molecular Biology.