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Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism.

M B Yaffe·M Schutkowski·M Shen·X Z Zhou·P T Stukenberg·J U Rahfeld·J Xu·J Kuang·M W Kirschner·G Fischer·L C Cantley·K P Lu
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Abstract

Pin1 is an essential and conserved mitotic peptidyl-prolyl isomerase (PPIase) that is distinct from members of two other families of conventional PPIases, cyclophilins and FKBPs (FK-506 binding proteins). In response to their phosphorylation during mitosis, Pin1 binds and regulates members of a highly conserved set of proteins that overlaps with antigens recognized by the mitosis-specific monoclonal antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPIase that specifically recognizes the phosphoserine-proline or phosphothreonine-proline bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar phosphorylated serine-proline-containing peptides, providing the basis for the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially isomerized proline residues preceded by phosphorylated serine or threonine with up to 1300-fold selectivity compared with unphosphorylated peptides. Pin1 may thus regulate mitotic progression by catalyzing sequence-specific and phosphorylation-dependent proline isomerization.

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Amino Acid IsomerasesAntibodies, MonoclonalBinding SitesCarrier ProteinsCell Cycle ProteinsDNA-Binding ProteinsEpitopesHeLa CellsHeat-Shock ProteinsHumansIsomerismMitosisModels, MolecularNIMA-Interacting Peptidylprolyl IsomeraseOligopeptidesPeptide LibraryPeptidylprolyl IsomerasePhosphoproteinsPhosphorylationPhosphoserinePhosphothreonineProlineProtein ConformationRecombinant Fusion ProteinsSubstrate SpecificityTacrolimus Binding ProteinsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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M B Yaffe, M Schutkowski, M Shen, X Z Zhou, P T Stukenberg, J U Rahfeld, J Xu, J Kuang, M W Kirschner, G Fischer, L C Cantley, K P Lu. 1997-12-12. Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism.. https://doi.org/10.1126/science.278.5345.1957

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