Binding of protein kinase B to the plakin family member periplakin
| Autor: | Alida M.M. de Vries-Smits, Boudewijn M.T. Burgering, A. Pieter J. van den Heuvel, Jurgen Riedl, Kim M.T. de Bruyn, Pascale F. Dijkers, Pascale C. van Weeren |
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| Rok vydání: | 2002 |
| Předmět: |
Protein Serine-Threonine Kinases
Biology Protein Structure Secondary Cell Line 3-Phosphoinositide-Dependent Protein Kinases chemistry.chemical_compound Chlorocebus aethiops Tumor Cells Cultured Animals Humans Vimentin Amino Acid Sequence Phosphatidylinositol Transcription factor Protein kinase B Periplakin Conserved Sequence Sequence Deletion Plakin Binding Sites Kinase Plakins Cell Biology Actins Mitochondria Protein Structure Tertiary Rats Cell biology DNA-Binding Proteins Pleckstrin homology domain Cytoskeletal Proteins chemistry COS Cells Mutation cardiovascular system Phosphorylation Protein Binding Signal Transduction |
| Zdroj: | Journal of Cell Science. 115:3957-3966 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.00069 |
| Popis: | The serine/threonine kinase protein kinase B (PKB/c-Akt) acts downstream of the lipid kinase phosphoinositide 3-kinase (PI3K) and functions as an essential mediator in many growth-factor-induced cellular responses such as cell cycle regulation, cell survival and transcriptional regulation. PI3K activation generates 3′-phosphorylated phosphatidylinositol lipids(PtdIns3P) and PKB activation requires PtdIns3P-dependent membrane translocation and phosphorylation by upstream kinases. However PKB activation and function is also regulated by interaction with other proteins. Here we show binding of PKB to periplakin, a member of the plakin family of cytolinker proteins. Interaction between PKB and periplakin was mapped to part of the pleckstrin homology (PH) domain of PKB, which is probably not involved in lipid binding, and indeed binding to periplakin did not affect PKB activation. We therefore investigated the possibility that periplakin may act as a scaffold or localization signal for PKB. In cells endogenous periplakin localizes to different cellular compartments, including plasma membrane,intermediate filament structures, the nucleus and mitochondria. Overexpression of the C-terminal part of periplakin, encompassing the PKB binding region,results in predominant intermediate filament localization and little nuclear staining. This also resulted in inhibition of nuclear PKB signalling as indicated by inhibition of PKB-dependent Forkhead transcription factor regulation. These results suggest a possible role for periplakin as a localization signal in PKB-mediated signalling. |
| Databáze: | OpenAIRE |
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