Crossroads of PI3K and Rac pathways

Abstract

Rac and PI3Ks are intracellular signal transducers able to regulate multiple signaling pathways fundamental for cell behavior. PI3Ks are lipid kinases that produce phosphorylated lipids which, in turn, transduce extracellular cues within the cell, while Rac is a small G protein that impacts on actin organization. Compelling evidence indicates that in multiple circumstances the 2 signaling pathways appear intermingled. For instance, phosphorylated lipids produced by PI3Ks recruit and activate GEF and GAP proteins, key modulators of Rac function. Conversely, PI3Ks interact with activated Rac, leading to Rac signaling amplification. This review summarizes the molecular mechanisms underlying the cross-talk between Rac and PI3K signaling in 2 different processes, cell migration and ROS production.

Rho GTPases at the crossroad of signaling networks in mammals

“…C.C. Campa, E. Ciraolo, A. Ghigo, G. Germena and E. Hirsch 16 summarizes the molecular mechanisms underlying the cross-talk between Rac and PI3K signaling in two different processes, cell migration and reactive oxygen species (ROS) production.…”

PI3Kδ promotes CD4+ T‐cell interactions with antigen‐presenting cells by increasing LFA‐1 binding to ICAM‐1

“…6 These include numerous guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) that positively and negatively regulate small GTPases. 7 …”

Making Heads or Tails of It: Cell–Cell Adhesion in Cellular and Supracellular Polarity in Collective Migration

“…Although mostly known for regulating apicobasal epithelial polarity (Nelson 2009), these complexes promote front -rear polarization by mechanisms that include Scribble-mediated recruitment of bPIX (Audebert et al 2004;Osmani et al 2010) and assembly of the Par complex (Nelson 2009), which recruits the RacGEF Tiam-1, leading to Rac activation (Nishimura et al 2005;Pegtel et al 2007). In parallel, GEFs are locally activated by RTKs (Goicoechea et al 2014;Campa et al 2015). Activated Rac and cdc42 promote cell protrusion through lamellipodia and filopodia driven by actin polymerization, most prominently via the Arp2/3 complex and WAVE-family proteins (Ridley 2015).…”

“…Polarity initiated at the nascent front involves activation of phosphoinositide 3-kinase (PI3K) and the Rho family GTPases Rac and cdc42, reinforced by positive feedback loops (Campa et al 2015). Like all Rho GTPases, Rac and cdc42 cycle between an active, GTP-bound state, induced by guanine exchange factors (GEFs), and an inactive GDP-bound state, induced by GTPase-activating proteins (GAPs).…”