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H-Ras distribution and signaling in plasma-membrane microdomains are regulated by acylation and deacylation events.H-Ras distribution and signaling in plasma-membrane microdomains are regulated by acylation and deacylation events.Agudo-Ibáñez L, Herrero A, Barbacid M, Crespo P. Mol Cell Biol. 2015 Mar 16. 2015-03-15T23:00:00Z<div style="text-align:justify;"><br></div><p style="text-align:justify;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2"><span class="ms-rteThemeForeColor-2-5 ms-rteThemeFontFace-1 ms-rteFontSize-2" style="font-weight:bold;">Abstract</span><br></span></p><div style="color:#000000;font-family:-webkit-standard;text-align:justify;"><p style="margin-bottom:0.5em;font-size:1.04em;font-family:arial, helvetica, clean, sans-serif;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">H-Ras must adhere to the plasma membrane to be functional. This is accomplished by posttranslational modifications, including palmitoylation, a reversible process whereby H-Ras traffics between the plasma membrane and the Golgi complex. At the plasma membrane, H-Ras has been proposed to occupy distinct sublocations, depending on its activation status: lipid rafts/detergent-resistant membrane fractions when bound to GDP, diffusing to disordered membrane/soluble fractions in response to GTP loading. Herein, we demonstrate that H-Ras sublocalization is dictated by its degree of palmitoylation in a cell type-specific manner. Whereas H-Ras localizes to detergent-resistant membrane fractions in cells with low palmitoylation activity, it locates to soluble membrane fractions in lineages where it is highly palmitoylated. Interestingly, in both cases GTP loading results in H-Ras diffusing away from its original sublocalization. Moreover, tilting the equilibrium between palmitoylation and depalmitoylation processes can substantially alter H-Ras segregation and, subsequently, its biochemical and biological functions. Thus, the palmitoylation/depalmitoylation balance not only regulates H-Ras cycling between endomembranes and the plasma membrane but also serves as a key orchestrator of H-Ras lateral diffusion between different types of plasma membrane and thereby of H-Ras signaling.</span><br></p></div><p>​<span style="color:#474f51;font-family:"yanone kaffeesatz";font-size:18px;background-color:#ffffff;">[</span><a href="" style="color:#ed391b;margin:0px;padding:0px;border:0px;font-stretch:inherit;font-size:18px;line-height:inherit;font-family:"yanone kaffeesatz";vertical-align:baseline;background-color:#ffffff;">PubMed</a><span style="color:#474f51;font-family:"yanone kaffeesatz";font-size:18px;background-color:#ffffff;">]</span><br></p>49