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Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains.

To understand the role of the Yes-associated protein (YAP), binding partners of its WW1 domain were isolated by a yeast two-hybrid screen. One of the interacting proteins was identified as p53-binding protein-2 (p53BP-2). YAP and p53BP-2 interacted in vitro and in vivo using their WW1 and SH3 domains, respectively. The YAP WW1 domain bound to the YPPPPY motif of p53BP-2, whereas the p53BP-2 SH3 domain interacted with the VPMRLR sequence of YAP, which is different from other known SH3 domain-binding motifs. By mutagenesis, we showed that this unusual SH3 domain interaction was due to the presence of three consecutive tryptophans located within the betaC strand of the SH3 domain. A point mutation within this triplet, W976R, restored the binding selectivity to the general consensus sequence for SH3 domains, the PXXP motif. A constitutively active form of c-Yes was observed to decrease the binding affinity between YAP and p53BP-2 using chloramphenicol acetyltransferase/enzyme-linked immunosorbent assay, whereas the overexpression of c-Yes did not modify this interaction. Since overexpression of an activated form of c-Yes resulted in tyrosine phosphorylation of p53BP-2, we propose that the p53BP-2 phosphorylation, possibly in the WW1 domain-binding motif, might negatively regulate the YAP.p53BP-2 complex.

Pubmed ID: 11278422

Authors

  • Espanel X
  • Sudol M

Journal

The Journal of biological chemistry

Publication Data

April 27, 2001

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR45626
  • Agency: NCI NIH HHS, Id: CA45757

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins
  • Blotting, Western
  • Brain
  • Carrier Proteins
  • Cell Line
  • Chloramphenicol O-Acetyltransferase
  • DNA, Complementary
  • Enzyme-Linked Immunosorbent Assay
  • Gene Library
  • Glutathione Transferase
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphoproteins
  • Phosphorylation
  • Plasmids
  • Point Mutation
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Transfection
  • Tryptophan
  • Two-Hybrid System Techniques
  • Tyrosine
  • src Homology Domains