title: S100 protein translocation in response to extracellular S100 is mediated by receptor for advanced glycation endproducts in human endothelial cells.
abstract: The extracellular functions of S100 proteins have attracted more attention in recent years. S100 proteins are a group of calcium-binding proteins which exhibit cell- and tissue-specific expression, and different expression levels of members from this family have been observed in various pathological conditions. The reported extracellular functions of S100 proteins include the ability to enhance neurite outgrowth, involvement in inflammation, and motility of tumour cells. In our previous study, we reported translocation of S100A13 in response to the elevated intracellular calcium levels induced by angiotensin II. In order to investigate potential effects of extracellular S100A13, recombinant S100A13 was used here to stimulate human endothelial cells. Addition of extracellular S100A13 to the cells resulted in both endogenous protein translocation and protein uptake from the extracellular space. To test specificity of this effect, addition of various other S100 proteins was also performed. Interestingly, translocation of specific S100 proteins was only observed when the cells were stimulated with the same extracellular S100 protein. Since the receptor for advanced glycation end products (RAGE) is a putative cell surface receptor for S100 proteins and is involved in various signal transduction pathways, we next investigated the interaction between the receptor and extracellular S100 proteins. We show here that NF-kappaB which is a downstream regulator in RAGE-mediated transduction pathways can be activated by addition of extracellular S100 proteins, and translocation of S100 proteins was inhibited by soluble RAGE. These experiments suggest a common cell surface receptor for S100 proteins on endothelial cells even though intracellular translocation induced by extracellular S100 proteins is specific.
authors.affiliation: Department of Pediatrics, Division of Clinical Chemistry and Biochemistry, University of Zürich, Steinwiesstr. 75, CH-8032 Zurich, Switzerland.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Hsieh
authors.forename: Beat W
authors.initials: BW
authors.lastname: Schäfer
authors.forename: Bernd
authors.initials: B
authors.lastname: Weigle
authors.forename: Claus W
authors.initials: CW
authors.lastname: Heizmann
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D019921:Biotinylation; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064568:S100 Calcium Binding Protein beta Subunit; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D000067616:S100A12 Protein; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D009414:Nerve Growth Factors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; C511523:S100A13 protein, human; D000804:Angiotensin II; C077591:S100A4 protein, human