Proline-directed phosphorylation and isomerization in mitotic regulation and in Alzheimer's Disease

Bioessays. 2003 Feb;25(2):174-81. doi: 10.1002/bies.10223.


The reversible phosphorylation of proteins on serine/threonine residues preceding proline (Ser/Thr-Pro) is a major regulatory mechanism for the control of a series of cell cycle events. Although phosphorylation is thought to regulate protein function by inducing conformational changes, little is known about most of these conformational changes and their significance. Recent studies indicate that the conformation and function of a subset of these phosphorylated proteins are controlled by the prolyl isomerase Pin1 through isomerization of specific phosphorylated Ser/Thr-Pro bonds. Furthermore, compelling evidence supports the idea that proline-directed phosphorylation and subsequent isomerization play a critical role not only in cell cycle control, but also in the development of Alzheimer's disease, where postmitotic neurons display various cell cycle markers, especially mitotic events, prior to degeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Humans
  • Isomerism
  • Mitosis / physiology*
  • Models, Neurological
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neurons / metabolism
  • Neurons / pathology
  • Peptidylprolyl Isomerase / metabolism
  • Phosphorylation
  • Proline / metabolism*


  • NIMA-Interacting Peptidylprolyl Isomerase
  • Proline
  • PIN1 protein, human
  • Peptidylprolyl Isomerase