Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for tumorigenesis

Hao-Hsuan Jeng, Laura J Taylor and Dafna Bar-Sagi ()
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Hao-Hsuan Jeng: New York University School of Medicine
Laura J Taylor: New York University School of Medicine
Dafna Bar-Sagi: New York University School of Medicine

Nature Communications, 2012, vol. 3, issue 1, 1-8

Abstract: Abstract Mammalian cells contain three closely related ras genes, H-ras, K-ras and N-ras. Although in a given tumour type, oncogenic mutations are selectively observed in only one of the ras genes, the acquisition of the transformed phenotype has been shown to require the contribution of the normal products of the other ras genes. Here we demonstrate that oncogenic K-Ras promotes the activation of wild-type H- and N-Ras. This activation is mediated by oncogenic K-Ras-dependent allosteric stimulation of Sos and confers a growth advantage to oncogenic K-Ras harbouring cancer cells. These findings underscore the complementary functions of oncogenic and wild-type Ras in tumour cells and identify a potential new targeting strategy for Ras-driven tumours.

Date: 2012
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DOI: 10.1038/ncomms2173

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