Stimulation of erythroleukaemia cell differentiation by extracellular high-mobility group-box protein 1 is independent of the receptor for advanced glycation end-products.
In several cell types the binding of extracellular high-mobility group-box protein 1 (HMGB1) with the receptor for advanced glycation end-products (RAGE) induces cytoskeletal reorganization and cell motility. To establish whether RAGE is also involved in murine erythroleukaemia (MEL) cell differentiation stimulated by HMGB1, we have demonstrated that these cells express a 51 kDa protein identified as RAGE, and then we have produced stable transfectants overexpressing wild-type (wt) RAGE or a dominant negative (dn) RAGE mutant lacking the cytoplasmic domain to analyse the differentiation process in these cells. Several experimental findings indicated that RAGE was not involved in the MEL cell differentiation programme. This was also supported by the identical stimulatory effect exerted by HMGB1 on both wt- or dn-RAGE transfectants. We have also observed that HMGB1 binds a 65 kDa protein on the surface of MEL cells, supporting the hypothesis that alternative targets of HMGB1 are expressed on the MEL cell membrane and may be involved as mediators of its signalling.
Sparatore
Bianca
B
Biochemistry Section, Department of Experimental Medicine, University of Genoa, Viale Benedetto XV, 1-16132 Genoa, Italy. traspar@unige.it
Pedrazzi
Marco
M
Passalacqua
Mario
M
Gaggero
Deborah
D
Patrone
Mauro
M
Pontremoli
Sandro
S
Melloni
Edon
E
D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000502:physiology; D024243:HMGB1 Protein / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008024:Ligands; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D024243:HMGB1 Protein; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases