• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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


  • Espanel X
  • Sudol M


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