Phosphoserine/threonine-binding domains

Curr Opin Cell Biol. 2001 Apr;13(2):131-8. doi: 10.1016/s0955-0674(00)00189-7.

Abstract

Phosphorylation of proteins on serine and threonine residues has traditionally been viewed as a means to allosterically regulate catalytic activity. Research within the past five years, however, has revealed that serine/threonine phosphorylation can also directly result in the formation of multimolecular signaling complexes through specific interactions between phosphoserine/threonine (pSer/Thr)-binding modules and phosphorylated sequence motifs. pSer/Thr-binding proteins and domains currently include 14-3-3, WW domains, forkhead-associated domains, and, tentatively, WD40 repeats and leucine-rich regions. It seems likely that additional modules will be found in the future. The amino acid sequences recognized by these pSer/Thr-binding modules show partial overlap with the optimal phosphorylation motifs for different protein kinase subfamilies, allowing the formation of specific signaling complexes to be controlled through combinatorial interactions between particular upstream kinases and a particular binding module. The structural basis for pSer/Thr binding differs dramatically between 14-3-3 proteins, WW domains and forkhead-associated domains, suggesting that their pSer/Thr binding function was acquired through convergent evolution.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Humans
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphoserine / metabolism*
  • Phosphothreonine / metabolism*
  • Protein Structure, Tertiary

Substances

  • Phosphoproteins
  • Phosphothreonine
  • Phosphoserine