NEDD4 can be regulated by auto-inhibition which is then disrupted by phosphorylation at specific tyrosine residues.
This auto-inhibitory conformation can be disrupted by the presence of calcium, by proteins that bind to NEDD4 to prevent this conformation, or by phosphorylation of NEDD4 at specific tyrosine residues to activate NEDD4 ubiquitin ligase activity. 
