RRC ID 58660
Author Rodríguez-Fdez S, Citterio C, Lorenzo-Martín LF, Baltanás-Copado J, Llorente-González C, Corbalán-García S, Vicente-Manzanares M, Bustelo XR.
Title Phosphatidylinositol Monophosphates Regulate Optimal Vav1 Signaling Output.
Journal Cells
Abstract Phosphatidylinositol-5 phosphate (PI5P) and other mono-phosphoinositides (mono-PIs) play second messenger roles in both physiological and pathological conditions. Despite this, their intracellular targets and mechanisms of action remain poorly characterized. Here, we show that Vav1, a protein that exhibits both Rac1 GDP/GTP exchange and adaptor activities, is positively modulated by PI5P and, possibly, other mono-PIs. Unlike other phospholipid-protein complexes, the affinity and specificity of the Vav1-lipid interaction entail a new structural solution that involves the synergistic action of the Vav1 C1 domain and an adjacent polybasic tail. This new regulatory layer, which is not conserved in the Vav family paralogs, favors the engagement of optimal Vav1 signaling outputs in lymphocytes.
Volume 8(12)
Published 2019-12-16
DOI 10.3390/cells8121649
PII cells8121649
PMID 31888228
PMC PMC6952945
MeSH Animals Humans Jurkat Cells Mice Phosphatidylinositol Phosphates / metabolism* Phosphatidylinositols / metabolism Phosphorylation Protein Binding / physiology Proto-Oncogene Proteins c-vav / genetics Proto-Oncogene Proteins c-vav / metabolism* Signal Transduction / physiology T-Lymphocytes / metabolism rac1 GTP-Binding Protein / metabolism
IF 5.656
Times Cited 1
Human and Animal Cells DT40(RCB1464)