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Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism
M B Yaffe1, M Schutkowski, M Shen
1Department of Medicine Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Science (New York, N.Y.)
|January 7, 1998
Summary
Pin1, a unique peptidyl-prolyl isomerase (PPIase), regulates cell division by binding phosphorylated proteins. It specifically targets phosphoserine-proline bonds, influencing mitotic progression.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Pin1 is a crucial mitotic peptidyl-prolyl isomerase (PPIase), distinct from cyclophilins and FKBP families.
- Pin1 interacts with phosphorylated proteins during mitosis, including those recognized by the MPM-2 antibody.
Purpose of the Study:
- To characterize Pin1 as a phosphorylation-dependent PPIase.
- To investigate Pin1's specificity for phosphoserine-proline and phosphothreonine-proline bonds in mitotic phosphoproteins.
- To elucidate the molecular basis for Pin1's interaction with MPM-2 antigens.
Main Methods:
- Peptide selection assays using Pin1 and MPM-2 antibody.
- Enzymatic assays to measure proline isomerization rates on phosphorylated and unphosphorylated peptides.
Main Results:
- Pin1 specifically recognizes and binds phosphoserine-proline or phosphothreonine-proline bonds.
- Pin1 and MPM-2 recognize similar phosphorylated serine-proline-containing peptides.
- Pin1 exhibits up to 1300-fold selectivity for isomerizing proline residues preceded by phosphorylated serine or threonine.
Conclusions:
- Pin1 functions as a sequence-specific, phosphorylation-dependent PPIase.
- Pin1's substrate specificity is dictated by phosphorylated proline residues.
- Pin1 likely regulates mitotic progression through proline isomerization of specific mitotic phosphoproteins.