title: Differential modification of Ras proteins by ubiquitination.
abstract: Ras proteins are essential components of signal transduction pathways that control cell proliferation, differentiation, and survival. It is well recognized that the functional versatility of Ras proteins is accomplished through their differential compartmentalization, but the mechanisms that control their spatial segregation are not fully understood. Here we show that HRas is subject to ubiquitin conjugation, whereas KRas is refractory to this modification. The membrane-anchoring domain of HRas is necessary and sufficient to direct the mono- and diubiquitination of HRas. Ubiquitin attachment to HRas stabilizes its association with endosomes and modulates its ability to activate the Raf/MAPK signaling pathway. Therefore, differential ubiquitination of Ras proteins may control their location-specific signaling activities.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, New York 11794, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Jura
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scotto-Lavino
authors.forename: Aleksander
authors.initials: A
authors.lastname: Sobczyk
authors.forename: Dafna
authors.initials: D
authors.lastname: Bar-Sagi
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D011992:Endosomes / Q000378:metabolism; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D018631:ras Proteins; D008239:Lysine