Function of WW domains as phosphoserine- or phosphothreonine-binding modules

Protein-interacting modules help determine the specificity of signal transd uction events, and protein phosphorylation can modulate the assembly of suc h modules into specific signaling complexes. Although phosphotyrosine-bindi ng modules have been well-characterized, phosphoserine- or phosphothreonine -binding modules have not been described. WW domains are small protein modu les found in various proteins that participate in cell signaling or regulat ion, WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiq uitin ligase Nedd4 bound to phosphoproteins, including physiological substr ates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with pro perties similar to those of SRC homology 2 domains, Phosphoserine- or phosp hothreonine-binding activity was required for Pin1 to interact with its sub strates in vitro and to perform its essential function in vivo.