Critical role of WW domain phosphorylation in regulating phosphoserine binding activity and Pin1 function

Pei Jung Lu, Xiao Zhen Zhou, Yih Cherng Liou, Joseph P. Noel, Kun Ping Lu

Research output: Contribution to journalArticlepeer-review

192 Citations (Scopus)

Abstract

Phosphoserine-binding modules help determine the specificity of signal transduction events. One such module, the group IV WW domain, plays an essential role in targeting the phosphorylation-specific prolyl isomerase Pin1 to its substrates. These modules require Ser/Thr phosphorylation of their ligands for binding activity. However, phosphorylation of these modules and its functional significance have not been described, nor is it known whether the function of Pin1 is regulated. Here we show that Pin1 WW domain is phosphorylated on Ser16 both in vitro and in vivo. Further, this phosphorylation regulates the ability of the WW domain to mediate Pin1 substrate interaction and cellular localization. Moreover, both Pin1 and WW domain mutants refractory to Ser16 phosphorylation act as dominant-negative mutants to induce mitotic block and apoptosis and increase multinucleated cells with 8 N DNA content. Thus, phosphorylation is a new mechanism critical for regulating WW domain phosphoserine binding activity and Pin1 function.

Original languageEnglish
Pages (from-to)2381-2384
Number of pages4
JournalJournal of Biological Chemistry
Volume277
Issue number4
DOIs
Publication statusPublished - 2002 Jan 25

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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