title: Regulating the regulator: post-translational modification of RAS.
abstract: RAS proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which regulate the activation state of RAS without covalently modifying it. By contrast, post-translational modifications (PTMs) of RAS proteins direct them to various cellular membranes and, in some cases, modulate GTP-GDP exchange. Important RAS PTMs include the constitutive and irreversible remodelling of its carboxy-terminal CAAX motif by farnesylation, proteolysis and methylation, reversible palmitoylation, and conditional modifications, including phosphorylation, peptidyl-prolyl isomerisation, monoubiquitylation, diubiquitylation, nitrosylation, ADP ribosylation and glucosylation.
authors.affiliation: NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Ahearn
authors.forename: Kevin
authors.initials: K
authors.lastname: Haigis
authors.forename: Dafna
authors.initials: D
authors.lastname: Bar-Sagi
authors.forename: Mark R
authors.initials: MR
authors.lastname: Philips
mesh_terms: D000818:Animals; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D051379:Mice; D011499:Protein Processing, Post-Translational; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D018631:ras Proteins