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
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, Y.
Right arrow Articles by Feng, G.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, Y.
Right arrow Articles by Feng, G.-S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2004, p. 1531-1539, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1531-1539.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Role of Gab1 in UV-Induced c-Jun NH2-Terminal Kinase Activation and Cell Apoptosis

Yingqing Sun,1 Jing Yuan,1 Houqi Liu,1,{dagger} Zhongqing Shi,1 Kelly Baker,1 Kristiina Vuori,1 Jie Wu,2 and Gen-Sheng Feng1*

Cancer Research Center, The Burnham Institute, La Jolla, California 92037,1 Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 336122

Received 3 November 2003/ Accepted 11 November 2003

Exposure of mammalian cells to UV irradiation leads to activation of the c-Jun NH2-terminal protein kinase (JNK) pathway, which is associated with cell apoptosis. However, the molecular mechanism for JNK activation by UV exposure is not fully understood. We show here an essential role of a multisubstrate adapter, Gab1, in this signaling cascade. Gab1-deficient mouse fibroblast cells were defective in induction of JNK activity by UV exposure or heat shock, and this defect was rescued by reintroduction of Gab1 into Gab1-/- cells. Consistently, Gab1-/- cells displayed reduced caspase 3 induction and apoptotic cell death in response to UV irradiation. Gab1 was constitutively complexed with JNK and became tyrosine phosphorylated in UV-irradiated cells. Genetic and pharmaceutical analyses suggest the involvement of c-Met and the Src family tyrosine kinases in mediating UV-induced Gab1 phosphorylation as well as JNK activation. In aggregate, these observations identify a new function of Gab1 in the response of mammalian cells to UV light.

* Corresponding author. Mailing address: The Burnham Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 713-6265. Fax: (858) 713-6274. E-mail: gfeng{at}burnham.org.

{dagger} Present address: Center of Developmental Biology, and Medical School of the Army, Shanghai, People’s Republic of China.

Molecular and Cellular Biology, February 2004, p. 1531-1539, Vol. 24, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.4.1531-1539.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cao, C., Huang, X., Han, Y., Wan, Y., Birnbaumer, L., Feng, G.-S., Marshall, J., Jiang, M., Chu, W.-M. (2009). G{alpha}i1 and G{alpha}i3 Are Required for Epidermal Growth Factor-Mediated Activation of the Akt-mTORC1 Pathway. Sci Signal 2: ra17-ra17 [Abstract] [Full Text]  
  • Petti, L. M., Ricciardi, E. C., Page, H. J., Porter, K. A. (2008). Transforming signals resulting from sustained activation of the PDGF{beta} receptor in mortal human fibroblasts. J. Cell Sci. 121: 1172-1182 [Abstract] [Full Text]  
  • Bard-Chapeau, E. A., Yuan, J., Droin, N., Long, S., Zhang, E. E., Nguyen, T. V., Feng, G.-S. (2006). Concerted Functions of Gab1 and Shp2 in Liver Regeneration and Hepatoprotection. Mol. Cell. Biol. 26: 4664-4674 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»