Protein kinase B/Akt acts via glycogen synthase kinase 3 to regulate recycling of  αvβ3 and α5β1 integrins

Roberts, M. S., Woods, A. J., Dale, Trevor Clive ORCID: https://orcid.org/0000-0002-4880-9963, van der Sluijs, P. and Norman, J. C. 2004. Protein kinase B/Akt acts via glycogen synthase kinase 3 to regulate recycling of  αvβ3 and α5β1 integrins. Molecular and Cellular Biology 24 (4) , pp. 1505-1515. 10.1128/MCB.24.4.1505-1515.2004

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Abstract

Protein kinase B (PKB)/Akt is known to promote cell migration, and this may contribute to the enhanced invasiveness of malignant cells. To elucidate potential mechanisms by which PKB/Akt promotes the migration phenotype, we have investigated its role in the endosomal transport and recycling of integrins. Whereas the internalization of αvβ3 and α5β1 integrins and their transport to the recycling compartment were independent of PKB/Akt, the return of these integrins (but not internalized transferrin) to the plasma membrane was regulated by phosphatidylinositol 3-kinases and PKB/Akt. The blockade of integrin recycling and cell spreading on integrin ligands effected by inhibition of PKB/Akt was reversed by inhibition of glycogen synthase kinase 3 (GSK-3). Moreover, expression of nonphosphorylatable active GSK-3β mutant GSK-3β-A9 suppressed recycling of α5β1 and αvβ3 and reduced cell spreading on ligands for these integrins, indicating that PKB/Akt promotes integrin recycling by phosphorylating and inactivating GSK-3. We propose that the ability of PKB/Akt to act via GSK-3 to promote the recycling of matrix receptors represents a key mechanism whereby integrin function and cell migration can be regulated by growth factors.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	American Society for Microbiology
ISSN:	0270-7306
Funders:	Cancer Research UK
Date of Acceptance:	3 November 2003
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/61740

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