GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Cells Année : 2021

GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior

Résumé

In adult stem cells, Glycogen Synthase Kinase 3 beta (GSK3 beta) is at the crossroad of signaling pathways controlling survival, proliferation, adhesion and differentiation. The microenvironment plays a key role in the regulation of these cell functions and we have demonstrated that the GSK3 beta activity is strongly dependent on the engagement of integrins and protease-activated receptors (PARs). Downstream of the integrin alpha(5)beta(1) or PAR(2) activation, a molecular complex is organized around the scaffolding proteins RACK1 and beta-arrestin-2 respectively, containing the phosphatase PP2A responsible for GSK3 beta activation. As a consequence, a quiescent stem cell phenotype is established with high capacities to face apoptotic and metabolic stresses. A protective role of GSK3 beta has been found for hematopoietic and intestinal stem cells. Latters survived to de-adhesion through PAR(2) activation, whereas formers were protected from cytotoxicity through alpha(5)beta(1) engagement. However, a prolonged activation of GSK3 beta promoted a defect in epithelial regeneration and a resistance to chemotherapy of leukemic cells, paving the way to chronic inflammatory diseases and to cancer resurgence, respectively. In both cases, a sexual dimorphism was measured in GSK3 beta-dependent cellular functions. GSK3 beta activity is a key marker for inflammatory and cancer diseases allowing adjusted therapy to sex, age and metabolic status of patients.
Fichier principal
Vignette du fichier
Racaud-C-2021.pdf (605.85 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03181357 , version 1 (25-03-2021)

Licence

Paternité

Identifiants

Citer

Claire Racaud-Sultan, Nathalie Vergnolle. GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior. Cells, 2021, 10 (2), ⟨10.3390/cells10020225⟩. ⟨hal-03181357⟩
34 Consultations
40 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More