title: CaM interaction and Ser181 phosphorylation as new K-Ras signaling modulators.
abstract: The small G-protein Ras was the first oncogene to be identified and has a very important contribution to human cancer development (20-23% prevalence). K-RasB, one of the members of the Ras family, is the one that is most mutated and plays a prominent role in pancreatic, colon and lung cancer development. Ras proteins are membrane bound GTPases that cycle between inactive, GDP-bound and active, GTP-bound, states. Most of the research into K-RasB activity regulation has focused on the analysis of how GTP-exchange factors (GEFs) and GTPase activating proteins (GAPs) are regulated by external and internal signals. In contrast, oncogenic K-RasB has a very low GTPase activity and furthermore is not deactivated by GAPs. Consequently, the consensus was that activity of oncogenic K-RasB was not modulated. In this extra view we recapitulate some recent data showing that calmodulin binding to K-RasB inhibits phosphorylation of K-RasB at Ser181, near to the membrane anchoring domain, modulating signaling of both non-oncogenic and oncogenic K-RasB. This may be relevant to normal cell physiology, but also opens new therapeutic perspectives for the inhibition of oncogenic K-RasB signaling in tumors.
authors.affiliation: Departament de Biologia Cel·lular, Immunologia i Neurociències; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Facultat de Medicina; Universitat de Barcelona; Barcelona, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Alvarez-Moya
authors.forename: Carles
authors.initials: C
authors.lastname: Barceló
authors.forename: Francesc
authors.initials: F
authors.lastname: Tebar
authors.forename: Montserrat
authors.initials: M
authors.lastname: Jaumot
authors.forename: Neus
authors.initials: N
authors.lastname: Agell