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Molecular and Cellular Biology, March 2002, p. 1352-1359, Vol. 22, No. 5
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.5.1352-1359.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Integrin {alpha}2ß1 Promotes Activation of Protein Phosphatase 2A and Dephosphorylation of Akt and Glycogen Synthase Kinase 3ß

Johanna Ivaska,1 Liisa Nissinen,1 Nina Immonen,1 John E. Eriksson,2 Veli-Matti Kähäri,3 and Jyrki Heino1,4*

MediCity and Department of Medical Biochemistry,1 Department of Dermatology and Center for Biotechnology, University of Turku, FIN-20520 Turku,3 Department of Biology, University of Turku, FIN-20014 Turku,2 Department of Biology, University of Jyväskylä, FIN-40351 Jyväskylä, Finland4

Received 27 April 2001/ Returned for modification 8 June 2001/ Accepted 27 November 2001

Serine/threonine kinase Akt is a downstream effector protein of phosphatidylinositol-3-kinase (PI-3K). Many integrins can function as positive modulators of the PI-3K/Akt pathway. Integrin {alpha}2ß1 is a collagen receptor that has been shown to induce specific signals distinct from those activated by other integrins. Here, we found that, in contrast what was found for cells adherent to fibronectin, {alpha}2ß1-mediated cell adhesion to collagen leads to dephosphorylation of Akt and glycogen synthase kinase 3ß (GSK3ß) and concomitantly to the induction of protein serine/threonine phosphatase 2A (PP2A) activity. PP2A activation can be inhibited by mutation in the {alpha}2 cytoplasmic domain and by a function-blocking anti-{alpha}2 antibody. Akt can be coprecipitated with PP2A, and coexpression of Akt with PP2Ac (catalytic subunit) inhibits Akt kinase activity. Integrin {alpha}2ß1-related activation of PP2A is dependent on Cdc42. These results indicate that cell adhesion to collagen modulates Akt activity via the {alpha}2ß1-induced activation of PP2A.

* Corresponding author. Mailing address: MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland. Phone: 358-2-333 7005. Fax: 358-2-333 7000. E-mail: jyrki.heino{at}utu.fi.

Molecular and Cellular Biology, March 2002, p. 1352-1359, Vol. 22, No. 5
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.5.1352-1359.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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