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 Hamann, M. J.
Right arrow Articles by Billadeau, D. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hamann, M. J.
Right arrow Articles by Billadeau, D. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2007, p. 1380-1393, Vol. 27, No. 4
0270-7306/07/$08.00+0     doi:10.1128/MCB.01608-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Asef2 Functions as a Cdc42 Exchange Factor and Is Stimulated by the Release of an Autoinhibitory Module from a Concealed C-Terminal Activation Element{triangledown}

Michael J. Hamann, Casey M. Lubking, Doris N. Luchini, and Daniel D. Billadeau*

Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905

Received 28 August 2006/ Returned for modification 17 October 2006/ Accepted 27 November 2006

Asef (herein called Asef1) was identified as a Rac1-specific exchange factor stimulated by adenomatous polyposis coli (APC), contributing to colorectal cancer cell metastasis. We investigated Asef2, an Asef1 homologue having a similar N-terminal APC binding region (ABR) and Src-homology 3 (SH3) domain. Contrary to previous reports, we found that Asef1 and Asef2 exchange activity is Cdc42 specific. Moreover, the ABR of Asef2 did not function independently but acted in tandem with the SH3 domain to bind APC. The ABRSH3 also bound the C-terminal tail of Asef2, allowing it to function as an autoinhibitory module within the protein. Deletion of the C-terminal tail did not constitutively activate Asef2 as predicted; rather, a conserved C-terminal segment was required for augmented Cdc42 GDP/GTP exchange. Thus, Asef2 activation involves APC releasing the ABRSH3 from the C-terminal tail, resulting in Cdc42 exchange. These results highlight a novel exchange factor regulatory mechanism and establish Asef1 and Asef2 as Cdc42 exchange factors, providing a more appropriate context for understanding the contribution of APC in establishing cell polarity and migration.

* Corresponding author. Mailing address: Mayo Clinic, Division of Oncology Research, 200 First Street SW, Rochester, MN 55905. Phone: (507) 266-4334. Fax: (507) 266-5146. E-mail: billadeau.daniel{at}mayo.edu.

{triangledown} Published ahead of print on 4 December 2006.

Molecular and Cellular Biology, February 2007, p. 1380-1393, Vol. 27, No. 4
0270-7306/07/$08.00+0     doi:10.1128/MCB.01608-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nolz, J. C., Nacusi, L. P., Segovis, C. M., Medeiros, R. B., Mitchell, J. S., Shimizu, Y., Billadeau, D. D. (2008). The WAVE2 complex regulates T cell receptor signaling to integrins via Abl- and CrkL-C3G-mediated activation of Rap1. JCB 182: 1231-1244 [Abstract] [Full Text]  
  • Itoh, R. E., Kiyokawa, E., Aoki, K., Nishioka, T., Akiyama, T., Matsuda, M. (2008). Phosphorylation and activation of the Rac1 and Cdc42 GEF Asef in A431 cells stimulated by EGF. J. Cell Sci. 121: 2635-2642 [Abstract] [Full Text]  
  • Bulk, E., Hascher, A., Liersch, R., Mesters, R. M., Diederichs, S., Sargin, B., Gerke, V., Hotfilder, M., Vormoor, J., Berdel, W. E., Serve, H., Muller-Tidow, C. (2008). Adjuvant Therapy with Small Hairpin RNA Interference Prevents Non-Small Cell Lung Cancer Metastasis Development in Mice. Cancer Res. 68: 1896-1904 [Abstract] [Full Text]  
  • Aoki, K., Taketo, M. M. (2007). Adenomatous polyposis coli (APC): a multi-functional tumor suppressor gene. J. Cell Sci. 120: 3327-3335 [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»