title: Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism.
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.
authors.affiliation: Department of Medicine Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Yaffe
authors.forename: M
authors.initials: M
authors.lastname: Schutkowski
authors.forename: M
authors.initials: M
authors.lastname: Shen
authors.forename: X Z
authors.initials: XZ
authors.lastname: Zhou
authors.forename: P T
authors.initials: PT
authors.lastname: Stukenberg
authors.forename: J U
authors.initials: JU
authors.lastname: Rahfeld
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Kuang
authors.forename: M W
authors.initials: MW
authors.lastname: Kirschner
authors.forename: G
authors.initials: G
authors.lastname: Fischer
authors.forename: L C
authors.initials: LC
authors.lastname: Cantley
authors.forename: K P
authors.initials: KP
authors.lastname: Lu
mesh_terms: D000591:Amino Acid Isomerases / Q000378:metabolism; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D000939:Epitopes; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007536:Isomerism; D008938:Mitosis; D008958:Models, Molecular; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D019151:Peptide Library; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011392:Proline / Q000378:metabolism*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D022021:Tacrolimus Binding Proteins
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000939:Epitopes; D006360:Heat-Shock Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009842:Oligopeptides; D019151:Peptide Library; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D010769:Phosphothreonine; D010768:Phosphoserine; D011392:Proline; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase