Editors' ChoiceProtein Trafficking

K-Ras Basically Travels in Different Circles

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Science's STKE  28 Mar 2000:
Vol. 2000, Issue 25, pp. tw8
DOI: 10.1126/stke.2000.25.tw8

Two motifs are required for the proper localization of H-Ras proteins to the plasma membrane: (i) a COOH-terminal CAAX motif that becomes farnesylated, and (ii) COOH-terminal proximal cysteine residues that become palmitoylated. However, although K-Ras is farnesylated, it is not palmitoylated, and instead has a region of basic lysine residues located near its COOH-terminus that statically interacts with the plasma membrane. Apolloni et al. used chimeric Ras proteins fused to green fluorescent protein and determined that palmitoylated Ras proteins travel through the exocytic pathway before reaching the plasma membrane. These palmitoylated proteins remained in the Golgi when the cells were incubated at 15°C or treated with Brefeldin A (BFA). However, Ras proteins that were only farnesylated and contained the basic region did not traverse through the Golgi and accumulated at the plasma membrane-even when cells were incubated at 15°C or treated with BFA. Farnesylated Ras proteins lacking a second signal accumulated in the Golgi, indicating that the basic region may be required to direct K-Ras away from the exocytic pathway. The function of H-Ras, but not K-Ras, is dependent on its localization to lipid rafts on the plasma membrane, and this may partially explain the biochemical differences between Ras proteins. The process of palmitoylation may ensure that H-Ras ends up within these lipid rafts. Thus, the formation of lipid rafts and the correct insertion of signaling proteins within them, may occur in the Golgi to ensure proper proximity of the proteins at the plasma membrane.

Apolloni, A., Prior, I.A., Lindsay, M., Parton, R.G., and Hancock, J.F. (2000) H-Ras but not K-Ras traffics to the plasma membrane through the exocytic pathway. Mol. Cell. Biol. 20: 2475-2487. [Abstract] [Full Text]

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