Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos
- PMID: 17486115
- DOI: 10.1038/ncb1594
Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos
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 acid interacts with a defined site in the Sos PH domain with high affinity and specificity. This interaction is essential for epidermal growth factor (EGF)-induced Sos membrane recruitment and Ras activation. Our findings establish a crucial role for PLD2 in the coupling of extracellular signals to Sos-mediated Ras activation, and provide new insights into the spatial coordination of this activation event.
Comment in
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PA promoted to manager.Nat Cell Biol. 2007 Jun;9(6):615-7. doi: 10.1038/ncb0607-615. Nat Cell Biol. 2007. PMID: 17541412 No abstract available.
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