New structural and functional insight into the regulation of Ras.
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.
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S1A8, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S1A8, Canada.
Yoshihito
Y
Kano
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S1A8, Canada.
Jonathan D
JD
Cook
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S1A8, Canada.
Jeffrey E
JE
Lee
Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S1A8, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S1A8, Canada. Electronic address: michael.ohh@utoronto.ca.
Michael
M
Ohh
D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism*
D018631:ras Proteins
GTPase cycle; Ras; Shp2; Src; Y32