Lysine Conservation and Context in TGFβ and Wnt Signaling Suggest New Targets and General Themes for Posttranslational ModificationReportar como inadecuado

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Journal of Molecular Evolution

, Volume 67, Issue 4, pp 323–333

First Online: 17 September 2008Received: 06 May 2008Revised: 11 July 2008Accepted: 07 August 2008


TGFβ 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 TGFβ 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.

KeywordsPhylogenetics TGFβ Smads Frizzled Dishevelled Ubiquitination Sumoylation Charlotte E. Konikoff and Robert G. Wisotzkey contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s00239-008-9159-4 contains supplementary material, which is available to authorized users.

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Autor: Charlotte E. Konikoff - Robert G. Wisotzkey - Stuart J. Newfeld


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