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Light Chain 3 associates with a Sos1 guanine nucleotide exchange factor: its significance in the Sos1-mediated Rac1 signaling leading to membrane ruffling

Oncogene volume 21, pages 7060–7066 (2002)Cite this article

Abstract

A 19 kDa protein was identified to associate with the Dbl oncogene homology domain of Sos1 (Sos–DH) and was purified from rat brains by GST–Sos–DH affinity chromatography. Peptide sequencing revealed that the protein is identical to light chain 3 (LC3), a microtubule-associated protein. LC3 coimmunoprecipitated with Sos1, and GST–LC3 was capable of forming complexes with Sos1 in in vitro GST-pull down assay. Furthermore, LC3 was colocalized with Sos1 in cells, as determined by immunohistochemistry. While Sos1 stimulated the guanine nucleotide exchange reaction on Rac1, LC3 suppressed the ability of Sos1 to activate Rac1 in in vitro experiments using COS cell lysates. Consistent with this, overexpression of LC3 decreased the level of active GTP-bound Rac1 in COS cells. Sos1 expression induced membrane ruffling, a downstream target for Rac1, but LC3 expression inhibited this biological effect of Sos1. These findings suggest that LC3 interacts with Sos1 and thereby negatively regulates the Sos1-dependent Rac1 activation leading to membrane ruffling

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Acknowledgements

We thank Drs D Lowy, K Kaibuchi and M Tanaka for the generous gifts of plasmid DNAs. We thank Dr T Yoshimori for providing anti-LC3 antibodies and Dr K Hirose for valuable discussions and encouragement. We are grateful to Drs T Takenawa and H Yamaguchi for the excellent technical assistance with confocal microscopy. We also thank Miss C Wada for preparation of the manuscript. This research was supported by the National Cancer Institute, NIH, DBS and DHHS under contract with ABL and by Terumo Life Science Foundation.

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Authors and Affiliations

  1. Department of Molecular Biology and Biochemistry, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan

    Shuichi Furuta, Wei Hao Shang, Aki Oshima & Tohru Kamata

  2. IRSP, SAIC Frederick, National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, 21702, Maryland, MD, USA

    Koichi Miura & Tohru Kamata

  3. Wlodawer's Program in Structural Biology, National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, 21702, Maryland, MD, USA

    Terry Copeland

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  1. Shuichi Furuta
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Correspondence to Tohru Kamata.

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Furuta, S., Miura, K., Copeland, T. et al. Light Chain 3 associates with a Sos1 guanine nucleotide exchange factor: its significance in the Sos1-mediated Rac1 signaling leading to membrane ruffling. Oncogene 21, 7060–7066 (2002). https://doi.org/10.1038/sj.onc.1205790

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