Binding to syntenin-1 protein defines a new mode of ubiquitin-based interactions regulated by phosphorylation.
J Biol Chem
; 286(45): 39606-14, 2011 Nov 11.
Article
in En
| MEDLINE
| ID: mdl-21949238
ABSTRACT
Syntenin-1 is a PDZ domain-containing adaptor that controls trafficking of transmembrane proteins including those associated with tetraspanin-enriched microdomains. We describe the interaction of syntenin-1 with ubiquitin through a novel binding site spanning the C terminus of ubiquitin, centered on Arg(72), Leu(73), and Arg(74). A conserved LYPSL sequence in the N terminus, as well as the C-terminal region of syntenin-1, are essential for binding to ubiquitin. We present evidence for the regulation of this interaction through syntenin-1 dimerization. We have also established that syntenin-1 is phosphorylated downstream of Ulk1, a serine/threonine kinase that plays a critical role in autophagy and regulates endocytic trafficking. Importantly, Ulk1-dependent phosphorylation of Ser(6) in the LYPSL prevents the interaction of syntenin-1 with ubiquitin. These results define an unprecedented ubiquitin-dependent pathway involving syntenin-1 that is regulated by Ulk1.
Full text:
1
Database:
MEDLINE
Main subject:
Protein Serine-Threonine Kinases
/
Ubiquitin
/
Intracellular Signaling Peptides and Proteins
/
Syntenins
/
Protein Multimerization
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2011
Type:
Article
Affiliation country:
United kingdom