Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms.
Mol Cell Biol
; 22(11): 3717-28, 2002 Jun.
Article
in En
| MEDLINE
| ID: mdl-11997508
ABSTRACT
It is widely accepted that cyclic AMP (cAMP) can block cell growth by phosphorylating Raf-1 on serine 43 and inhibiting signaling to extracellular signal-regulated protein kinase. We show that the suppression of Raf-1 by cAMP is considerably more complex than previously reported. When cellular cAMP is elevated, Raf-1 is phosphorylated on three residues (S43, S233, and S259), which work independently to block Raf-1. Both Ras-dependent and Ras-independent processes are disrupted. However, when cAMP-insensitive versions of Raf-1 are expressed in NIH 3T3 cells, their growth is still strongly suppressed when cAMP is elevated. Thus, although Raf-1 appears to be an important cAMP target, other pathways are also targeted by cAMP, providing alternative mechanisms that lead to suppression of cell growth.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Division
/
Cyclic AMP
/
Proto-Oncogene Proteins c-raf
Limits:
Animals
Language:
En
Journal:
Mol Cell Biol
Year:
2002
Type:
Article
Affiliation country:
United kingdom