Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins.

Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Abstract Text:

Mingguang Li,P Todd Stukenberg,David L Brautigan,Mingguang Li,P Todd Stukenberg,David L Brautigan,

Inhibitor-2 (I-2) is the most ancient protein that selectively recognizes type-1 protein phosphatase and is phosphorylated by CDK1-cyclinB during mitosis at Thr72 in a conserved PXTP site. Pin1 is a peptide prolyl cis/trans isomerase conserved among eukaryotes that specifically reacts with proteins phosphorylated at Ser/Thr-Pro sites. We tested phospho-T72-I-2 as a substrate for Pin1 and discovered that unphosphorylated I-2 bound Pin1 with micromolar affinity and phosphorylation of the PXTP site or truncation of I-2 reduced binding 10-fold. Ectopic Pin1 coprecipitated endogenous I-2 and ectopic I-2 coprecipitated endogenous Pin1, but only in the absence of detergents, which may account for the interaction not being detected previously. Endogenous I-2 and Pin1 colocalized in HeLa cells and showed nuclear-cytoplasmic redistribution in response to cell density, suggestive of their association in living cells. Recombinant Pin1 binding to different phosphoproteins in mitotic cell extracts was modulated by I-2, and binding to individual mitotic phosphoproteins was increased, decreased or unaffected by I-2, showing that I-2 allosterically modifies Pin1 specificity. This was confirmed by mutation of Ser16 to Ala in the Pin1 WW domain that eliminated I-2 binding and abrogated I-2 effects on Pin1 binding to different phosphoproteins. A S16E mutation to mimic Pin1 phosphorylation restored binding to both I-2 and phospho-T72-I-2, indicating that phosphorylation of both proteins governs their interaction. The results reveal a novel function for I-2, and suggest phosphorylation-dependent regulation of Pin1 specificity during entry and exit of mitosis, in other phases of the cell cycle, and in multiple cell signaling processes.

Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Publishing Authors By Initials

M Li,PT Stukenberg,DL Brautigan,M Li,PT Stukenberg,DL Brautigan,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemistry

VOLUME: 47

Page Numbers: 292-300

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 7

MONTH: 12

YEAR: 2007

Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins.

AFFILIATION: Center for Cell Signaling, Department of Microbiology, and Department of Biochemistry & Molecular Genetics, University of Virginia School of Medicine Charlottesville, Virginia 22908.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Biochemistry

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins Related Publications

• Assembly of MYPT1 with protein phosphatase-1 in fibroblasts redirects localization and reorganizes the actin cytoskeleton.
• Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins.
• Maternal phosphatase inhibitor-2 is required for proper chromosome segregation and mitotic synchrony during Drosophila embryogenesis.
• Phosphorylation and functions of inhibitor-2 family of proteins.
• Protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains.
• TAB4 Stimulates TAK1-TAB1 Phosphorylation and Binds Polyubiquitin to Direct Signaling to NF-{kappa}B.