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Molecular and Cellular Biology, April 2009, p. 1933-1943, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01707-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

An Adaptor Role for Cytoplasmic Sam68 in Modulating Src Activity during Cell Polarization{triangledown}

Marc-Étienne Huot,1 Claire M. Brown,2 Nathalie Lamarche-Vane,3 and Stéphane Richard1*

Terry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Departments of Oncology and Medicine, McGill University, Montréal, Québec, Canada H3T 1E2,1 Life Sciences Complex Imaging Facility and Department of Biochemistry, McGill University, Montréal, Québec, Canada H3G 1Y6,2 Department of Anatomy and Cell Biology, McGill University, Montréal, Québec, Canada H3A 2B23

Received 5 November 2008/ Returned for modification 8 December 2008/ Accepted 5 January 2009

The Src-associated substrate during mitosis with a molecular mass of 68 kDa (Sam68) is predominantly nuclear and is known to associate with proteins containing the Src homology 3 (SH3) and SH2 domains. Although Sam68 is a Src substrate, little is known about the signaling pathway that link them. Src is known to be activated transiently after cell spreading, where it modulates the activity of small Rho GTPases. Herein we report that Sam68-deficient cells exhibit loss of cell polarity and cell migration. Interestingly, Sam68-deficient cells exhibited sustained Src activity after cell attachment, resulting in the constitutive tyrosine phosphorylation and activation of p190RhoGAP and its association with p120rasGAP. Consistently, we observed that Sam68-deficient cells exhibited deregulated RhoA and Rac1 activity. By using total internal reflection fluorescence microscopy, we observed Sam68 near the plasma membrane after cell attachment coinciding with phosphorylation of its C-terminal tyrosines and association with Csk. These findings show that Sam68 localizes near the plasma membrane during cell attachment and serves as an adaptor protein to modulate Src activity for proper signaling to small Rho GTPases.

* Corresponding author. Mailing address: Segal Cancer Centre, 3755 Côte Ste.-Catherine Road, Montréal, Québec H3T 1E2, Canada. Phone: (514) 340-8260. Fax: (514) 340-8295. E-mail: stephane.richard{at}mcgill.ca

{triangledown} Published ahead of print on 12 January 2009.

Molecular and Cellular Biology, April 2009, p. 1933-1943, Vol. 29, No. 7
0270-7306/09/$08.00+0     doi:10.1128/MCB.01707-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Huot, M.-E., Vogel, G., Richard, S. (2009). Identification of a Sam68 Ribonucleoprotein Complex Regulated by Epidermal Growth Factor. J. Biol. Chem. 284: 31903-31913 [Abstract] [Full Text]  


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