FIGURE 3.

Kv1.3 regulates cell proliferation independently from ion conductance: the «voltage sensor model». Changes in the plasma membrane potential, that occur during cell cycle progression or upon application of external stimuli, induce a conformational change in Kv1.3 due to its voltage-sensor domain. Because Kv1.3 interacts with other proteins in large complexes (the so-called Kv1.3 channelosome), these conformational changes translate into phosphorylation of the C-terminus of Kv1.3 and activation of pro-proliferative signal transduction cascades, including integrin and growth factor receptor (GFR) signaling. These events result in activation of Ras, which activates the Raf/Mitogen-activated protein kinase kinase (MEK)/Extracellular signal-Regulated Kinase (ERK) pathway, finally leading to proliferation mediated by different downstream transcription factors (TF) such as c-Myc (Pérez-Garcìa et al., 2018). This figure was created using images from Servier Medical Art (http://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.