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  • Original Paper
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Interactions of c-Raf-1 with phosphatidylserine and 14-3-3

Oncogene volume 18, pages 3862–3869 (1999)Cite this article

Abstract

Activation of Raf-1 occurs at the plasma membrane. We recently showed that 14-3-3 must be complexed with Raf-1 for efficient recruitment to the plasma membrane and activation by Ras, but that 14-3-3 is completely displaced from Raf-1 following plasma membrane binding. We show here that the Raf-1 zinc finger is not absolutely required for 14-3-3 binding but is required to stabilize the interaction between Raf-1 and 14-3-3. Incubation of Raf-1 with phosphatidylserine, an inner plasma membrane phospholipid, results in removal of 14-3-3 and an increase in Raf-1 kinase activity, whereas removal of 14-3-3 from Raf-1 using specific phosphopeptides substantially reduces Raf-1 basal kinase activity. Displacement of 14-3-3 from activated Raf-1 by phosphopeptides has no effect on kinase activity if Raf-1 is first removed from solution, but completely eradicates kinase activity of soluble activated Raf-1. These results suggest a mechanism for the removal of 14-3-3 from Raf-1 at the plasma membrane and show that removal of 14-3-3 from Raf-1 has markedly different effects depending on experimental conditions.

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Acknowledgements

This work was supported by a grant from the National Health and Medical Research Council of Australia. JF Hancock is also supported by the Royal Children's Hospital Foundation, Queensland.

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  1. Department of Pathology, Queensland Cancer Fund Laboratory for Experimental Oncology, University of Queensland Medical School, Herston, 4006, Queensland, Australia

    Robert A McPherson, Angus Harding, Sandrine Roy, Annette Lane & John F Hancock

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McPherson, R., Harding, A., Roy, S. et al. Interactions of c-Raf-1 with phosphatidylserine and 14-3-3. Oncogene 18, 3862–3869 (1999). https://doi.org/10.1038/sj.onc.1202730

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