The Mechanism(s) of Ras Activation: Where? How?… and how long?
Ponente: Ignacio Rubio
University of Jena [Jena, Germany]
Host: Eugenio Santos
Fecha: 25/05/2017 - 25/05/2017
Salón de Actos del CIC
Ras activation by growth factors and other cues is tightly regulated in intensity, time and space. For example the subcellular distribution and trafficking of the three Ras proteins K-Ras, H-Ras, N-Ras is thought to have a major impact on the duration and the quality of the signal. Analogously, the timely control of Ras activity is considered to be important for cell-fate decision making. Thus, Ras activation in cells emerging from quiescence in response to growth factor is typically very short-lived as a transient versus prolongued Ras-signal is appears to be essential for driving cells into the cell cycle. The accumulation of active Ras-GTP following hormonal stimulation is understood in some detail: It results from the up-regulation of nucleotide exchange on Ras via the growth factor induced enhancement of nucleotide exchange factor (GEF) activity. In most settings other than leukocytes and neuronal cells this step involves the ubiquitously expressed GEF Sos. By contrast the mechanisms involved in the subsequent Ras inactivation, i.e. the ensuing reversion of Ras-GTP levels back to basal values, are mostly unknown. Our laboratory has investigated various aspects related to the spatio-temporal control of Ras activation, which I will present in the seminar. IN addition, I will present findings obtained in a separate project in which we developed a tool for the acute inhibition of Ras and which has proved instrumental for the analysis of Ras signalling at distinct phases of the cell cycle.