Activated release of membrane-anchored TGF-alpha in the absence of cytosol.
J Cell Biol
; 122(1): 95-101, 1993 Jul.
Article
in En
| MEDLINE
| ID: mdl-8314849
ABSTRACT
The ectodomain of proTGF-alpha, a membrane-anchored growth factor, is converted into soluble TGF-alpha by a regulated cellular proteolytic system that recognizes proTGF-alpha via the C-terminal valine of its cytoplasmic tail. In order to define the biochemical components involved in proTGF-alpha cleavage, we have used cells permeabilized with streptolysin O (SLO) that have been extensively washed to remove cytosol. PMA, acting through a Ca(2+)-independent protein kinase C, activates cleavage as efficiently in permeabilized cells as it does in intact cells. ProTGF-alpha cleavage is also stimulated by GTP gamma S through a mechanism whose pharmacological properties suggest the involvement of a heterotrimeric G protein acting upstream of the PMA-sensitive Ca(2+)-independent protein kinase C. Activated proTGF-alpha cleavage is dependent on ATP hydrolysis, appears not to require vesicular traffic, and acts specifically on proTGF-alpha that has reached the cell surface. These results indicate that proTGF-alpha is cleaved from the cell surface by a regulated system whose signaling, recognition, and proteolytic components are retained in cells devoid of cytosol.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Precursors
/
Protein Processing, Post-Translational
/
Transforming Growth Factor alpha
/
Aluminum Compounds
/
GTP-Binding Proteins
/
Fluorides
Limits:
Animals
Language:
En
Journal:
J Cell Biol
Year:
1993
Document type:
Article