Function of WW domains as phosphoserine- or phosphothreonine-binding modules.
Protein-interacting modules help determine the specificity of signal transduction events, and protein phosphorylation can modulate the assembly of such modules into specific signaling complexes. Although phosphotyrosine-binding modules have been well-characterized, phosphoserine- or phosphothreonine-binding modules have not been described. WW domains are small protein modules found in various proteins that participate in cell signaling or regulation. WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner. The Pin1 WW domain functioned as a phosphoserine- or phosphothreonine-binding module, with properties similar to those of SRC homology 2 domains. Phosphoserine- or phosphothreonine-binding activity was required for Pin1 to interact with its substrates in vitro and to perform its essential function in vivo.
Cancer Biology Program, Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
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D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D006367:HeLa Cells; D006801:Humans; D008025:Ligases; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D000075702:Nedd4 Ubiquitin Protein Ligases; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010748:Phosphopeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism*; D010769:Phosphothreonine / Q000378:metabolism*; D017354:Point Mutation; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases; D020687:cdc25 Phosphatases
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010748:Phosphopeptides; D010750:Phosphoproteins; D010769:Phosphothreonine; D010768:Phosphoserine; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; D044767:Ubiquitin-Protein Ligases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; D008025:Ligases