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

  • Science. 1997 Dec 12;278(5345):1957-60. doi: 10.1126/science.278.5345.1957.
M B Yaffe  1 ,  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
Affiliations
  • 1. Department of Medicine Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
PMID: 9395400 DOI: 10.1126/science.278.5345.1957
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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