NR ALCO
AU Stahl,N.; Boulton,T.G.; Ip,N.; Davis,S.; Yancopoulos,G.D.
TI The tails of two proteins: the scrapie prion protein and the ciliary neurotrophic factor receptor.
QU Brazilian Journal of Medical and Biological Research 1994 Feb; 27(2): 297-301
PT journal article
AB Many proteins with a variety of functions have proven to have glycosylphosphatidylinositol (GPI)-linkages; two members of this family are the scrapie prion protein and the receptor for ciliary neurotrophic factor (CNTF). The scrapie prion protein has two isoforms: PrPc is found in brain cells from normal animals, while PrPsc is an abnormal isoform that is only found in scrapie-infected animals. PrPsc is the only identified component of the prion, an infectious agent that apparently does not contain nucleic acid. Models for how prions replicate require that PrPsc must somehow recruit PrPc and catalyze or stabilize a post-translational event that converts PrPc into PrPsc. Extensive characterization has suggested that this critical post-translational event is probably conformational and not a chemical change. The presence of a GPI anchor on CNTFR alpha is an unusual feature for a molecule that must transmit a signal to the inside of the cell. Recent data have indicated that CNTFR alpha must bind CNTF, then interact with two other "beta" receptor components to initiate signal transduction. Furthermore, we have shown that, unlike the vast majority of receptors, CNTFR alpha can function as a soluble molecule to promote CNTF action on cells that contain the two beta components, but do not themselves express CNTFR alpha. Intriguingly, we have also demonstrated that CNTFR alpha is present in cerebrospinal fluid and blood in vivo, and the release of CNTFR alpha from skeletal muscle is increased by denervation of the muscle. Whether the soluble form is released through GPI-anchor cleavage remains to be determined.
IN (Review) Das Scrapie-Prionprotein besitzt Glykosylphosphatidylinositol-Anhänge. Das abnorm modifizierte Prionprotein ist die einzige identifizierte Komponente der Scrapie-Prione, welche keine Nukleinsäure zu enthalten scheinen.
MH Animal; Ciliary Neurotrophic Factor; Glycosylphosphatidylinositols/chemistry/*metabolism/physiology; Nerve Tissue Proteins/chemistry/*metabolism/physiology; Prions/chemistry/*metabolism; Protein Processing, Post-Translational; Receptors, Growth Factor/*metabolism/physiology; Signal Transduction
AD Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
SP englisch
PO Brasilien