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Identification of Kinase-substrate Pairs Using High Throughput Screening
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Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase

Xiao-Ru Chen1, Tatyana I Igumenova1

  • 1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, 77843, USA.

Advances in Biological Regulation
|December 10, 2022
PubMed

Insights

The peptidyl-prolyl isomerase Pin1 regulates cancer pathways by binding to phosphorylated sites on kinases. Pin1

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • The peptidyl-prolyl isomerase Pin1 (Pin1) is crucial for regulating oncogenic pathways.
  • Pin1 targets phosphorylated Ser/Thr-Pro motifs, catalyzing cis-trans isomerization.
  • This isomerization affects protein stability, activity, and localization.

Purpose of the Study:

  • To survey eukaryotic protein kinases regulated by Pin1.
  • To identify and analyze Pin1 binding sites within these kinases.
  • To understand the role of Pin1 in kinase regulation and oncogenesis.

Main Methods:

  • Survey of eukaryotic protein kinases.
  • Identification of Pin1 binding sites.
  • Analysis of Pin1 target site locations within kinase structures.

Main Results:

  • Pin1 target sites in kinases are located in catalytic, C-terminal, and regulatory domains, not exclusively in disordered regions.
  • Kinases downregulated by Pin1 can be tumor-suppressing.
  • Kinases upregulated by Pin1 are functionally pro-oncogenic.

Conclusions:

  • Pin1's regulatory role extends to diverse locations within protein kinases.
  • Pin1 activity differentially impacts tumor-suppressing and pro-oncogenic kinases.
  • These findings support the development of Pin1 inhibitors for cancer therapy.
Keywords:
Cis-trans isomerizationEukaryotic protein kinaseOncogenic pathwayPeptidyl-prolyl isomerase Pin1Proline-directed protein kinaseTumor suppressor

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