Prenylation of Ras proteins is required for efficient hSOS1-promoted guanine nucleotide exchange - PubMed (original) (raw)

Comparative Study

. 1994 Sep 9;269(36):22672-7.

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Comparative Study

Prenylation of Ras proteins is required for efficient hSOS1-promoted guanine nucleotide exchange

E Porfiri et al. J Biol Chem. 1994.

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Abstract

We have studied whether hSOS1, a mammalian guanine nucleotide exchange factors responsible for activating Ras in response to growth factor stimulation, requires post-translational processing of Ras proteins to promote guanine nucleotide exchange. Our results showed that full-length hSOS1 catalyzed guanine nucleotide exchange on prenylated K-Ras(4B) but with a much lower efficiency on unprocessed K-Ras(4B). The apparent Km of hSOS1 for prenylated K-Ras(4B) was 225 (+/- 25) nM with a Vmax of 0.7 (+/- 0.1) mmol/min/mmol. The activity of hSOS1 against unprocessed K-Ras(4B) was too low to measure Km and Vmax. Consistent with these observations, full-length hSOS1 formed a complex with nucleotide-depleted prenylated K-Ras(4B) but not with unprocessed K-Ras(4B). A geranylgeranylated mutant of K-Ras(4B) was an equally good substrate for hSOS1 as wild-type farnesylated K-Ras. Similarly hSOS1 promoted guanine nucleotide exchange on prenylated Ha-Ras but showed minimal activity toward unprocessed Ha-Ras. Neither the polybasic domain of K-Ras (4B) or palmitoylation of Ha-Ras were required for hSOS1-promoted guanine nucleotide exchange. We attempted to identify a minimal region of hSOS1 capable of promoting guanine nucleotide exchange on both prenylated and unprocessed K-Ras. However, a truncated form of hSOS1 comprising only the CDC25 homology domain retained preferential catalytic activity against prenylated K-Ras, whereas the cognate domain from CDC25 was more active against unprocessed K-Ras.

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