Analysis of mammalian ras effector functions

Over the last 8 years or so, a great deal of effort has been put into understanding the biochemical function of the three mammalian p21ras proteins. Single-amino-acid alterations in these three proteins have been detected in 25-50% of some types of human cancers, and it is believed that the somatic mutational event that generated these amino acid substitutions is an important step in the development of these malignancies. The authors report here some of their efforts to look for a possible target for p21ras regulation. In a series of experiments, they have looked for ras-induced changes in another known second-messenger system, namely, the breakdown of phosphatidylinositol (PtdIns) lipids by a phospholipase C. The results lead to the conclusion that NIH-3T3 cells transformed by oncogenic p21ras have an increased basal phospholipase C activity. In a different approach to identify a target for ras, they have analyzed its interaction with the recently described cellular protein, GAP. They have shown that this protein appears to bind ras at a site previously identified as the effector site, strongly implicating GAP as the target protein for p21ras regulation