Lysine conservation and context in TGFbeta and Wnt signaling suggest new targets and general themes for posttranslational modification

J Mol Evol. 2008 Oct;67(4):323-33. doi: 10.1007/s00239-008-9159-4. Epub 2008 Sep 17.

Abstract

TGFbeta and Wnt pathways play important roles in the development of animals from sponges to humans. In both pathways posttranslational modification as a means of regulating their function, such as lysine modification by ubiquitination and sumoylation, has been observed. However, a gap exists between the immunological observation of posttranslational modification and the identification of the target lysine. To fill this gap, we conducted a phylogenetic analysis of lysine conservation and context in TGFbeta and Wnt pathway receptors and signal transducers and suggest numerous high-probability candidates for posttranslational modification. Further comparison of results from both pathways suggests two general features for biochemical regulation of intercellular signaling: receptors are less frequent targets for modification than signal transduction agonists, and a lysine adjacent to an upstream hydrophobic residue may be a preferred context for modification. Overall the results suggest numerous applications for an evolutionary approach to the biochemical regulation of developmental pathways, including (1) streamlining of the identification of the target lysine, (2) determination of when members of a multigene family acquire distinct activities, (3) application to any conserved protein family, and (4) application to any modification of a specific amino acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Amino Acid Sequence
  • Animals
  • Conserved Sequence*
  • Dishevelled Proteins
  • Frizzled Receptors / chemistry
  • Lysine / chemistry*
  • Molecular Sequence Data
  • Phosphoproteins / chemistry
  • Protein Processing, Post-Translational*
  • Receptors, Transforming Growth Factor beta / chemistry
  • Signal Transduction*
  • Smad Proteins / chemistry
  • Transforming Growth Factor beta / metabolism*
  • Wnt Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Dishevelled Proteins
  • Frizzled Receptors
  • Phosphoproteins
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta
  • Wnt Proteins
  • Lysine