Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo.
It has recently been reported that Ki-Ras protein can be modified in vitro by farnesylation or geranylgeranylation. However, a previous analysis of Ki-Ras prenylation in vivo found only farnesylated Ki-Ras. In this report it is shown that under normal conditions, Ki-Ras is farnesylated in vivo and when cells are treated with the farnesyl transferase inhibitors B956 or B957, farnesylation is inhibited and Ki-Ras becomes geranylgeranylated in a dose dependent manner. These results have strong implications in the design of anticancer drugs based on inhibition of prenylation.
Rowell
C A
CA
Eisai Research Institute, Andover, Massachusetts 01810, USA.
Kowalczyk
J J
JJ
Lewis
M D
MD
Garcia
A M
AM
D016475:3T3 Cells; D000818:Animals; D051379:Mice; D017368:Protein Prenylation; D018631:ras Proteins / Q000378:metabolism*
D018631:ras Proteins