Integrin alpha 2 beta 1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3 beta

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 2 beta 1 is a collagen receptor that has been shown to induce specific signals distinct from those activa...

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Bibliographic Details
Published in:Molecular and cellular biology 2002-03, Vol.22 (5), p.1352
Main Authors: Ivaska, Johanna, Nissinen, Liisa, Immonen, Nina, Eriksson, John E, Kähäri, Veli-Matti, Heino, Jyrki
Format: Article
Language:English
Subjects:
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
cdc42 GTP-Binding Protein - metabolism
Cell Adhesion
Cells, Cultured
Collagen
Enzyme Activation
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Humans
Integrins - metabolism
Mitogen-Activated Protein Kinases - metabolism
p38 Mitogen-Activated Protein Kinases
Phosphoprotein Phosphatases - metabolism
Protein Binding
Protein Phosphatase 2
Protein Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Receptors, Collagen
Signal Transduction
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Summary: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 2 beta 1 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 2 beta 1-mediated cell adhesion to collagen leads to dephosphorylation of Akt and glycogen synthase kinase 3 beta (GSK3 beta) 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 2 beta 1-related activation of PP2A is dependent on Cdc42. These results indicate that cell adhesion to collagen modulates Akt activity via the alpha 2 beta 1-induced activation of PP2A.
ISSN:0270-7306
DOI:10.1128/MCB.22.5.1352-1359.2002