Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and Tau proteins

Xiao Zhen Zhou, Oliver Kops, Andreas Werner, Pei Jung Lu, Minhui Shen, Gerlind Stoller, Gerhard Küllertz, Michael Stark, Gunter Fischer, Kun Ping Lu

Research output: Contribution to journalArticlepeer-review

453 Citations (Scopus)

Abstract

The reversible protein phosphorylation on serine or threonine residues that precede proline (pSer/Thr-Pro) is a key signaling mechanism for the control of various cellular processes, including cell division. The pSer/Thr-Pro moiety in peptides exists in the two completely distinct cis and trans conformations whose conversion is catalyzed specifically by the essential prolyl isomerase Pin1. Previous results suggest that Pin1 might regulate the conformation and dephosphorylation of its substrates. However, it is not known whether phosphorylation-dependent prolyl isomerization occurs in a native protein and/or affects dephosphorylation of pSer/Thr-Pro motifs. Here we show that the major Pro-directed phosphatase PP2A is conformation-specific and effectively dephosphorylates only the trans pSer/Thr-Pro isomer. Furthermore, Pin1 catalyzes prolyl isomerization of specific pSer/Thr-Pro motifs both in Cdc265C and tau to facilitate their dephosphorylation by PP2A. Moreover, Pin1 and PP2A show reciprocal genetic interactions, and prolyl isomerase activity of Pin1 is esential for cell division in vivo. Thus, phosphorylation-specific prolyl isomerization catalyzed by Pin1 is a novel mechanism essential for regulating dephosphorylation of certain pSer/Thr-Pro motifs.

Original languageEnglish
Pages (from-to)873-883
Number of pages11
JournalMolecular Cell
Volume6
Issue number4
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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