Calcium/calmodulin-dependent protein kinase II binds to Raf-1 and modulates integrin-stimulated ERK activation
| Autor: | K. Ulrich Bayer, Guido Rossi, Anna Lina Cavallo, Mario Vitale, Tiziana Di Matola, Gianfranco Fenzi, Maddalena Illario |
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| Přispěvatelé: | Illario, Maddalena, A. L., Cavallo, K. U., Bayer, T. D., Matola, Fenzi, Gianfranco, G., Rossi, M., Vitale, Cavallo, Al, Bayer, Ku, DI MATOLA, T, Rossi, G, Vitale, M., Fenzi, Gf, Rossi, Guido |
| Rok vydání: | 2003 |
| Předmět: |
MAPK/ERK pathway
Integrins Time Factors Calmodulin Integrin Blotting Western environment and public health Biochemistry Models Biological Cell Line Ca2+/calmodulin-dependent protein kinase Animals Humans Enzyme Inhibitors Phosphorylation Molecular Biology CAMK biology Dose-Response Relationship Drug Chemistry Kinase Cell Biology Precipitin Tests Cell biology Fibronectins Rats Enzyme Activation Proto-Oncogene Proteins c-raf enzymes and coenzymes (carbohydrates) Calcium-Calmodulin-Dependent Protein Kinases Cancer research biology.protein ras Proteins Calcium Signal transduction Mitogen-Activated Protein Kinases Calcium-Calmodulin-Dependent Protein Kinase Type 2 Protein Binding Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 278(46) |
| ISSN: | 0021-9258 |
| Popis: | Integrin activation generates different signalings in a cell type-dependent manner and stimulates cell proliferation through the Ras/Raf-1/Mek/Erk pathway. In this study, we demonstrate that integrin stimulation by fibronectin (FN), besides activating the Ras/Erk pathway, generates an auxiliary calcium signal that activates calmodulin and the Ca2+/calmodulin-dependent protein kinase II (CaMKII). This signal regulates Raf-1 activation by Ras and modulates the FN-stimulated extracellular signal-regulated kinase (Erk-1/2). The binding of soluble FN to integrins induced increase of intracellular calcium concentration associated with phosphorylation and activation of CaMKII. In two different cell lines, inhibition of CaMKII activity by specific inhibitors inhibited Erk-1/2 phosphorylation. Whereas CaMK inhibition affected neither integrin-stimulated Akt phosphorylation nor p21Ras or Mek-1 activity, it was necessary for Raf-1 activity. FN-induced Raf-1 activity was abrogated by the CaMKII specific inhibitory peptide ant-CaNtide. Integrin activation by FN induced the formation of a Raf-1/CaMKII complex, abrogated by inhibition of CaMKII. Active CaMKII phosphorylated Raf-1 in vitro. This is the first demonstration that CaMKII interplays with Raf-1 and regulates Erk activation induced by Ras-stimulated Raf-1. These findings also provide evidence supporting the possible existence of cross-talk between other intracellular pathways involving CaMKII and Raf-1. |
| Databáze: | OpenAIRE |
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