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Molecular and Cellular Biology, August 2005, p. 6485-6495, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6485-6495.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

SRC-1 Mediates UNC-5 Signaling in Caenorhabditis elegans

Jeeyong Lee,1,2 Weiquan Li,1,2 and Kun-Liang Guan1,2,3*

Life Sciences Institute,1 Department of Biological Chemistry,2 Institute of Gerontology, University of Michigan, Ann Arbor, Michigan 481093

Received 26 January 2005/ Returned for modification 2 March 2005/ Accepted 5 May 2005

The secreted molecule unc-6/netrin is important for guiding axon projections and cell migrations. unc-5 and unc-40/DCC are identified as receptors for unc-6/netrin. The downstream factors of unc-6 receptors are beginning to be elucidated, and some key factors have been identified in various organisms. Here, we showed that SRC-1 interacts with the cytosolic domain of UNC-5 through its SH2 domain. This interaction also requires the intact kinase activity of SRC-1. Downregulation of src-1 by RNA interference decreases the biological processes initiated by the UNC-5 protein and decreases UNC-5 tyrosine phosphorylation. We also generated a chimeric protein consisting of the extracellular domain and transmembrane domain of UNC-5 and an intracellular domain of SRC-1. This fusion protein is able to partially rescue mutant phenotypes caused by unc-5 but not unc-6, unc-40, and unc-34. Our results support a model in which SRC-1 is required for UNC-5-induced axon repulsion and gonad migration signaling pathways and in which localizing SRC-1 activity to UNC-5 is crucial for proper signal transduction in response to unc-6/netrin.

* Corresponding author. Mailing address: Life Sciences Institute, University of Michigan, 5450 Medical Science I Building, Ann Arbor, MI 48109-0606. Phone: (734) 763-3030. Fax: (734) 647-9702. E-mail: kunliang{at}umich.edu.

Molecular and Cellular Biology, August 2005, p. 6485-6495, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6485-6495.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Li, W., Aurandt, J., Jurgensen, C., Rao, Y., Guan, K.-L. (2006). FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5. J. Cell Sci. 119: 47-55 [Abstract] [Full Text]  
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