Home
Resources
Publications
The CAAX Peptidomimetic Compound B581 Specifically Blocks Farnesylated, but Not Geranylgeranylated or Myristylated, Oncogenic Ras Signaling and Transformation

The CAAX Peptidomimetic Compound B581 Specifically Blocks Farnesylated, but Not Geranylgeranylated or Myristylated, Oncogenic Ras Signaling and Transformation

A D Cox, A M Garcia, J K Westwick, J J Kowalczyk, M D Lewis, D A Brenner, C J Der

J Biol Chem. 1994 Jul 29;269(30):19203-6.

PMID: 8034681

Abstract:

Recently developed CAAX peptidomimetic compounds have been shown to be potent and specific inhibitors of farnesyl protein transferase activity and to block the growth of Ras-transformed cells. However, whether this growth inhibitory action is specifically a consequence of blocking oncogenic Ras signaling has not been determined. To address this question, we have utilized mutants of the normally farnesylated oncogenic Ras protein (Ras-F) that are modified by alternative lipids, a geranylgeranyl isoprenoid (Ras-GG) or the fatty acid myristate (Myr-Ras), to determine the specificity of the CAAX peptidomimetic compound, B581. Like Ras-F, both Ras-GG and Myr-Ras are membrane-associated and transforming. Unexpectedly, NIH 3T3 cells transformed by each of the three Ras mutants underwent morphological alteration to a less transformed, but not normal, morphology. However, B581 inhibited the ability of only Ras-F-transformed cells, but not Ras-GG- or Myr-Ras- (or Raf-) transformed cells, to grow in soft agar. Furthermore, although all three lipid-modified versions of Ras stimulated mitogen-activated protein kinase activation, and both Jun and Elk-1 transcriptional activity, B581 inhibited only farnesylated Ras activation of these three downstream components of Ras signaling. Therefore, B581 prevents the growth of Ras-transformed cells by specifically antagonizing Ras-mediated signaling.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP149759966	B581		149759-96-6	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: