NR AXBX
AU Americo,T.A.; Chiarini,L.B.; Linden,R.
TI Signaling induced by hop/STI-1 depends on endocytosis
QU Biochemical and Biophysical Research Communications 2007 Jun 29; 358(2): 620-5
PT journal article; research support, non-u.s. gov't
AB The co-chaperone hop/STI-1 is a ligand of the cell surface prion protein (PrPc), and their interaction leads to signaling and biological effects. Among these, hop/STI-1 induces proliferation of A172 glioblastoma cells, dependent on both PrPc and activation of the Erk pathway. We tested whether clathrin-mediated endocytosis affects signaling induced by hop/STI-1. Both hyperosmolarity induced by sucrose and monodansyl-cadaverine blocked Erk activity induced by hop/STI-1, without affecting the high basal Akt activity typical of A172. The endocytosis inhibitors also affected the sub-cellular distribution of phosphorylated Erk, with blockade of the latter's activity. The data indicate that signaling induced by hop/STI-1 depends on endocytosis. These findings are consistent with a role of sub-cellular trafficking in signal transduction following engagement by PrPc by ligands such as hop/STI-1, and may help unravel both the functions of the prion protein, as well as possible loss-of-function components of prion diseases.
MH Cell Line, Tumor; *Endocytosis; Glioblastoma/*metabolism; Homeodomain Proteins/*metabolism; Humans; PrPc Proteins/*metabolism; *Signal Transduction; Tumor Suppressor Proteins/*metabolism
AD Instituto de Biofisica da UFRJ, Centro de Ciencias da Saude, bloco G, Cidade Universitaria, Rio de Janeiro, Brazil.
SP englisch
PO USA