ABSTRACT The activation of Ras by the guanine nucleotide-exchange factor Son of sevenless (Sos) constitutes the rate-limiting step in the transduction process that links receptor tyrosine

kinases to Ras-triggered intracellular signalling pathways. A prerequisite for the function of Sos in this context is its ligand-dependent membrane recruitment, and the prevailing model

implicates both the Sos carboxy-terminal proline-rich motifs and amino-terminal pleckstrin homology (PH) domain in this process. Here, we describe a previously unrecognized pathway for the

PH domain-dependent membrane recruitment of Sos that is initiated by the growth factor-induced generation of phosphatidic acid via the signalling enzyme phospholipase D2 (PLD2). Phosphatidic

coordination of this activation event. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through

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Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS KRAS INTERACTION WITH RAF1 RAS-BINDING DOMAIN AND CYSTEINE-RICH DOMAIN PROVIDES INSIGHTS INTO RAS-MEDIATED RAF

ACTIVATION Article Open access 19 February 2021 REGULATION OF RAS PALMITOYLTRANSFERASES BY ACCESSORY PROTEINS AND PALMITOYLATION Article 05 January 2024 COMPOSITION OF RECEPTOR TYROSINE

KINASE-MEDIATED LIPID MICRO-DOMAINS CONTROLLED BY ADAPTOR PROTEIN INTERACTION Article Open access 17 March 2021 REFERENCES * Schlessinger, J. Cell signaling by receptor tyrosine kinases.

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Biol._ 16, 2173–2179 (2006). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS The authors thank members of the Bar-Sagi and Frohman laboratories, J. Kuriyan and H.

Sondermann for helpful discussion, S. McLaughlin for help with the lipid vesicle binding assay and L. Taylor for help with image capturing and analysis. This work was supported by research

grants from National Institutes of Health to D.B.-S. (CA55360 and CA28146), G.D. (GM071475) and M.A.F. (DK64166 and GM71520), and a Scientist Development Grant from the American Heart

Association to G.D. (0430096N). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Graduate Program in Genetics, Stony Brook University, Stony Brook, 11794, NY, USA Chen Zhao, Michael A. Frohman 

& Dafna Bar-Sagi * Department of Molecular Genetics and Microbiology Stony Brook University, Stony Brook, 11794, NY, USA Chen Zhao & Dafna Bar-Sagi * Department of Biochemistry, NYU

School of Medicine New York, 10016, NY, USA Chen Zhao * Department of Pharmacology and Center for Developmental Genetics, Stony Brook University, Stony Brook, 11794, NY, USA Guangwei Du 

& Michael A. Frohman * Department of Physiology and Biophysics, Stony Brook University, Stony Brook, 11794, NY, USA Karl Skowronek & Dafna Bar-Sagi Authors * Chen Zhao View author

publications You can also search for this author inPubMed Google Scholar * Guangwei Du View author publications You can also search for this author inPubMed Google Scholar * Karl Skowronek

View author publications You can also search for this author inPubMed Google Scholar * Michael A. Frohman View author publications You can also search for this author inPubMed Google Scholar

* Dafna Bar-Sagi View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS C.Z. and D.B-S. conceived and designed the experiments. C.Z. performed

the experiments. G.D. and M.A.F. designed, generated and provided PLD2 reagents. K.S. performed preliminary lipid-binding experiments. CORRESPONDING AUTHOR Correspondence to Dafna Bar-Sagi.

ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary figures S1, S2, S3 and S4 (PDF

249 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Zhao, C., Du, G., Skowronek, K. _et al._ Phospholipase D2-generated phosphatidic acid couples

EGFR stimulation to Ras activation by Sos. _Nat Cell Biol_ 9, 707–712 (2007). https://doi.org/10.1038/ncb1594 Download citation * Received: 21 February 2007 * Accepted: 17 April 2007 *

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