GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4 - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles EMBO Journal Year : 2012

GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4

Abstract

The molecular mechanisms by which receptors regulate the Ras Binding Domains of the PIP3-generating, class I PI3Ks remain poorly understood, despite their importance in a range of biological settings, including tumorigenesis, activation of neutrophils by pro-inflammatory mediators, chemotaxis of Dictyostelium and cell growth in Drosophila. We provide evidence that G protein-coupled receptors (GPCRs) can stimulate PLCb2/b3 and diacylglycerol- dependent activation of the RasGEF, RasGRP4 in neutrophils. The genetic loss of RasGRP4 phenocopies knock-in of a Ras-insensitive version of PI3Kc in its effects on PI3Kc-dependent PIP3 accumulation, PKB activation, chemokinesis and reactive oxygen species (ROS) formation. These results establish a new mechanism by which GPCRs can stimulate Ras, and the broadly important principle that PLCs can control activation of class I PI3Ks.
Fichier principal
Vignette du fichier
embo j hervé_1.pdf (968.23 Ko) Télécharger le fichier
Origin Files produced by the author(s)
Loading...

Dates and versions

hal-00776864 , version 1 (29-05-2020)

Identifiers

Cite

Sabine Suire Sabine, Charlotte Lécureuil, Karen Anderson E, George Damoulakis George, Izabella Niewczas Izabella, et al.. GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2/b3 and the RasGEF RasGRP4. EMBO Journal, 2012, 31 (14), pp.3118-3129. ⟨10.1038/emboj.2012.167⟩. ⟨hal-00776864⟩
93 View
96 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More