Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8309025 | Cellular Signalling | 2018 | 26 Pages |
Abstract
S100A6 is a calcium binding protein expressed mainly in fibroblasts and epithelial cells. Interestingly, S100A6 is also present in extracellular fluids. Recently we have shown that S100A6 is secreted by WJMS cells and binds to integrin β1 (Jurewicz et al., 2014). In this work we describe for the first time the mechanism of S100A6 secretion and signaling pathways activated by the S100A6-integrin β1 complex. We show that colchicine suppressed the release of S100A6 into the cell medium, which indicates that the protein might be secreted via a tubulin-dependent pathway. By applying double immunogold labeling and immunofluorescence staining we have shown that S100A6 associates with microtubules in WJMS cells. Furthermore, results obtained from immunoprecipitation and proximity ligation assay (PLA), and from in vitro assays, reveal that S100A6 is able to form complexes with α and β tubulin in these cells, and that the S100A6-tubulin interaction is direct. We have also found that the S100A6 protein, due to binding to integrin β1, activates integrin-linked kinase (ILK), focal adhesion kinase (FAK) and p21-activated kinase (PAK). Our results suggest that binding of S100A6 to integrin β1 affects cell adhesion/proliferation due to activation of ILK and FAK signaling pathways.
Keywords
GSK3βFAKDPBSPMSFDTTIPTGPLAPBS-TCCCPJnkSDSPAKRAGEcarbonyl cyanide chlorophenylhydrazonePBSEGFR4β-phorbol 12-myristate 13-acetateBSAc-Jun N-terminal kinasePMAPBS containing 0.05% Tween 20Proximity ligation assaybovine serum albuminILKisopropyl-β-d-thiogalactopyranosidedithiothreitolsodium dodecyl sulfateDulbecco's phosphate buffered salinePhosphate buffered salinephenylmethylsulfonyl fluoridelactate dehydrogenaseLDHp21-activated kinaseintegrin-linked kinasefocal adhesion kinaseGlycogen synthase kinase-3βReceptor for advanced glycation end productsEpidermal growth factor receptor
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Ewelina Jurewicz, Elżbieta Wyroba, Anna Filipek,