title: Plasma membrane regulates Ras signaling networks.
abstract: Ras GTPases activate more than 20 signaling pathways, regulating such essential cellular functions as proliferation, survival, and migration. How Ras proteins control their signaling diversity is still a mystery. Several pieces of evidence suggest that the plasma membrane plays a critical role. Among these are: (1) selective recruitment of Ras and its effectors to particular localities allowing access to Ras regulators and effectors; (2) specific membrane-induced conformational changes promoting Ras functional diversity; and (3) oligomerization of membrane-anchored Ras to recruit and activate Raf. Taken together, the membrane does not only attract and retain Ras but also is a key regulator of Ras signaling. This can already be gleaned from the large variability in the sequences of Ras membrane targeting domains, suggesting that localization, environment and orientation are important factors in optimizing the function of Ras isoforms.
authors.affiliation: Department of Medicinal Chemistry; University of Illinois at Chicago ; Chicago, IL USA.
authors.forename: Tanmay Sanjeev
authors.initials: TS
authors.lastname: Chavan
authors.affiliation: Center for Computational Biology and Bioinformatics; Koc University ; Istanbul, Turkey.
authors.forename: Serena
authors.initials: S
authors.lastname: Muratcioglu
authors.affiliation: Department of Biochemistry and Molecular Genetics; University of Illinois at Chicago ; Chicago, IL USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Marszalek
authors.affiliation: Cancer and Inflammation Program; Basic Science Program; Leidos Biomedical Research, Inc.; Frederick National Laboratory for Cancer Research; National Cancer Institute at Frederick ; Frederick, MD USA.
authors.forename: Hyunbum
authors.initials: H
authors.lastname: Jang
authors.affiliation: Center for Computational Biology and Bioinformatics; Koc University ; Istanbul, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Keskin
authors.affiliation: Center for Computational Biology and Bioinformatics; Koc University ; Istanbul, Turkey.
authors.forename: Attila
authors.initials: A
authors.lastname: Gursoy
authors.affiliation: Cancer and Inflammation Program; Basic Science Program; Leidos Biomedical Research, Inc.; Frederick National Laboratory for Cancer Research; National Cancer Institute at Frederick; Frederick, MD USA; Sackler Institute of Molecular Medicine; Department of Human Genetics and Molecular Medicine; Sackler School of Medicine; Tel Aviv University; Tel Aviv, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.affiliation: Department of Biochemistry and Molecular Genetics; University of Illinois at Chicago ; Chicago, IL USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Gaponenko
keywords: Ras GTPases; Ras oligomerization; Ras signaling; lipid rafts; membrane microdomains; plasma membrane