New structural and functional insight into the regulation of Ras. (October 2016)

• Record Type: Journal Article
• Authors: Kano, Yoshihito; Cook, Jonathan D.; Lee, Jeffrey E.; Ohh, Michael
• Is Part Of: Seminars in cell & developmental biology. Volume 58(2016)
• Page Start: 70
• Page End: 78
• Publication Date: 2016-10
• Subjects: Ras -- Y32 -- Src -- Shp2 -- GTPase cycle; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2016.06.006
• Languages: English
• ISSNs: 1084-9521

Abstract

Abstract: Mutations in RAS and various components of the Ras signaling pathways are among the most common causative genetic alterations in human cancers, accounting up to 25% of lung cancers and over 90% of pancreatic cancers. Ras is a small GTPase that functions as a 'molecular switch' in a number of signaling pathways that regulate vital eukaryotic cellular functions. Despite our comprehensive understanding of the molecular mechanisms governing the activity of Ras, the clinical outcome of various pharmacologic anti-cancer strategies designed to directly inactivate Ras have been less than satisfactory. In this review, the more recently uncovered mode of regulation of Ras involving non-receptor tyrosine kinase and phosphatase, which have long been suspected of contributing to the oncogenic potential of Ras, will be discussed in the context of both function and structure.