title: FBP WW domains and the Abl SH3 domain bind to a specific class of proline-rich ligands.
abstract: WW domains are conserved protein motifs of 38-40 amino acids found in a broad spectrum of proteins. They mediate protein-protein interactions by binding proline-rich modules in ligands. A 10 amino acid proline-rich portion of the morphogenic protein, formin, is bound in vitro by both the WW domain of the formin-binding protein 11 (FBP11) and the SH3 domain of Abl. To explore whether the FBP11 WW domain and Abl SH3 domain bind to similar ligands, we screened a mouse limb bud expression library for putative ligands of the FBP11 WW domain. In so doing, we identified eight ligands (WBP3 through WBP10), each of which contains a proline-rich region or regions. Peptide sequence comparisons of the ligands revealed a conserved motif of 10 amino acids that acts as a modular sequence binding the FBP11 WW domain, but not the WW domain of the putative signal transducing factor, hYAP65. Interestingly, the consensus ligand for the FBP11 WW domain contains residues that are also required for binding by the Abl SH3 domain. These findings support the notion that the FBP11 WW domain and the Abl SH3 domain can compete for the same proline-rich ligands and suggest that at least two subclasses of WW domains exist, namely those that bind a PPLP motif, and those that bind a PPXY motif.
authors.affiliation: Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA 02115, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Bedford
authors.forename: D C
authors.initials: DC
authors.lastname: Chan
authors.forename: P
authors.initials: P
authors.lastname: Leder
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins; D016384:Consensus Sequence; D003429:Cross Reactions; D050556:Fatty Acid-Binding Proteins; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism*; D000080865:Formins; D008024:Ligands; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D016415:Sequence Alignment; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000091102:YAP-Signaling Proteins; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050556:Fatty Acid-Binding Proteins; D005326:Fetal Proteins; C106410:Fnbp1 protein, mouse; D000080865:Formins; D008024:Ligands; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D016374:Oncogene Proteins v-abl; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D011392:Proline; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn