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

Abstract : 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.
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https://hal.inrae.fr/hal-03181357
Contributor : Nathalie Seguin <>
Submitted on : Thursday, March 25, 2021 - 3:27:32 PM
Last modification on : Friday, June 4, 2021 - 2:40:26 PM

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

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