PrPcactivation induces neurite outgrowth and differentiation in PC12 cells: role for caveolin-1 in the signal transduction pathway
| Autor: | Guido Camici, Paolo Cirri, Paolo De Paoli, Chiara Bini, Barbara Pantera, Giampaolo Manao, Anna Caselli |
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| Rok vydání: | 2009 |
| Předmět: |
Integrins
Cell signaling Neurogenesis Cellular differentiation Caveolin 1 Biology Proto-Oncogene Proteins c-fyn PC12 Cells Second Messenger Systems Biochemistry CSK Tyrosine-Protein Kinase Cellular and Molecular Neuroscience chemistry.chemical_compound FYN Neurites Animals PrPC Proteins Phosphorylation Extracellular Signal-Regulated MAP Kinases Brain Cell Differentiation Tyrosine phosphorylation Protein-Tyrosine Kinases Rats Cell biology src-Family Kinases chemistry Focal Adhesion Protein-Tyrosine Kinases Second messenger system ras Proteins raf Kinases Signal transduction Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Neurochemistry. 110:194-207 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | Cellular prion protein (PrP(c)) is a ubiquitous glycoprotein, whose physiological role is poorly characterized. It has been suggested that PrP(c) participates in neuritogenesis, neuroprotection, copper metabolism, and signal transduction. In this study we detailed the intracellular events induced by PrP(c) antibody-mediated cross-linking in PC12 cells. We found a Fyn-dependent activation of the Ras-Raf pathway, which leads to a rapid and transient phosphorylation of extracellular regulated kinases. In addition, this activation cascade relies on the engagement of integrins, and involves focal adhesion kinase activation. We demonstrated the tyrosine phosphorylation of caveolin-1 as a consequence of PrP(c) stimulation, and showed that phosphocaveolin-1 scaffolds and coordinates protein complexes involved in PrP(c)-dependent signaling. Moreover, we found that caveolin-1 phosphorylation, is a mechanism for recruiting the C-terminal Src kinase and inactivating Fyn, so as to terminate cell signaling. Furthermore our data support a significant role for PrP(c) as a response mediator in neuritogenesis and cell differentiation. |
| Databáze: | OpenAIRE |
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