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Title: Signaling induced by hop/STI-1 depends on endocytosis

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [1];  [1]
  1. Instituto de Biofisica da UFRJ, Centro de Ciencias da Saude, bloco G, Cidade Universitaria, 21941-902 Rio de Janeiro (Brazil)

The co-chaperone hop/STI-1 is a ligand of the cell surface prion protein (PrP{sup C}), and their interaction leads to signaling and biological effects. Among these, hop/STI-1 induces proliferation of A172 glioblastoma cells, dependent on both PrP{sup C} 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, consistent 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 PrP{sup C} by ligands such as hop/STI-1, and may help help unravel both the functions of the prion protein, as well as possible loss-of-function components of prion diseases.

OSTI ID:
20991419
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 358, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2007.04.202; PII: S0006-291X(07)00919-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English

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