Editors' ChoiceReview

Many More Miles in Ras Research

Science's STKE  11 Apr 2000:
Vol. 2000, Issue 27, pp. tw3
DOI: 10.1126/stke.2000.27.tw3

As mature as the field of Ras research is, there are still numerous questions to posit and answers to pursue. Indeed, how much we know reveals how little we understand. Shields et al. delineate five areas of Ras research that require more work if we are to understand the interconnected nature of the pathways Ras activates. The five areas addressed include the following: (i) the difference between Raf-dependent and Raf-independent signals, (ii) the function of Rho family guanosine triphosphatases (GTPases) in Ras-mediated transformation, (iii) the cell-type differences in response to Ras activation, (iv) the individual roles of the different Ras proteins, and (v) how current methods may obfuscate our understanding of the physiological role of Ras. The authors discuss the different post-translational modifications of the H-, K-, and N-Ras proteins with regard to plasma membrane localization and the differences in their ability to activate specific signaling pathways. Also of interest, Shields et al. raise concerns over the proper use of overexpression and dominant-negative experiments and whether the observations specifically answer the experimentally designed questions.

Shields, J.M., Pruitt, K., McFall, A., Shaub, A., and Der, C.J. (2000) Understanding Ras: 'it ain't over 'til it's over'. Trends Cell Biol. 10:147-154. [Online Journal]