Ras Partners (original) (raw)

1. L. Van Aelst,
2. M.A. White, and
3. M.H. Wigler
4. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724

Excerpt

RAS PROBLEM

The RAS oncogenes were first discovered as the transforming elements of acutely oncogenic retroviruses. Subsequently, cellular RAS genes were found to be frequently activated by mutation in a wide variety of human cancers, providing the first example of a common oncogenic mechanism. As a consequence, Ras proteins have been studied extensively (for review, see Barbacid 1987).

RAS genes are found ubiquitously in eukaryotic organisms. They encode low-molecular-weight guanine nucleotide-binding proteins that hydrolyze GTP and localize to the inner surface of the plasma membrane after undergoing elaborate carboxy-terminal processing. Proteins that are involved in processing Ras, or in regulating its activity, e.g., by accelerating guanine nucleotide hydrolysis or exchange, have been largely conserved in evolution (for review, see Wigler 1993).

Understanding the function of Ras has been more difficult. Genetic and biochemical studies point to the involvement of Ras in regulating protein kinases in vertebrate cells and in the...