title: Pin1: Intimate involvement with the regulatory protein kinase networks in the global phosphorylation landscape.
abstract: BACKGROUND
  Protein phosphorylation is a universal regulatory mechanism that involves an extensive network of protein kinases. The discovery of the phosphorylation-dependent peptidyl-prolyl isomerase Pin1 added an additional layer of complexity to these regulatory networks.
  
  
  METHODS
  We have evaluated interactions between Pin1 and the regulatory kinome and proline-dependent phosphoproteome taking into consideration findings from targeted studies as well as data that has emerged from systematic phosphoproteomic workflows and from curated protein interaction databases.
  
  
  CONCLUSIONS
  The relationship between Pin1 and the regulatory protein kinase networks is not restricted simply to the recognition of proteins that are substrates for proline-directed kinases. In this respect, Pin1 itself is phosphorylated in cells by protein kinases that modulate its functional properties. Furthermore, the phosphorylation-dependent targets of Pin1 include a number of protein kinases as well as other enzymes such as phosphatases and regulatory subunits of kinases that modulate the actions of protein kinases.
  
  
  CONCLUSIONS
  As a result of its interactions with numerous protein kinases and their substrates, as well as itself being a target for phosphorylation, Pin1 has an intricate relationship with the regulatory protein kinase and phosphoproteomic networks that orchestrate complex cellular processes and respond to environmental cues. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets.
authors.affiliation: Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1; Department of Oncology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1. Electronic address: litchfi@uwo.ca.
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
authors.affiliation: Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1; Department of Oncology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Shilton
authors.affiliation: Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1; Department of Oncology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Brandl
authors.affiliation: Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1; Department of Oncology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5C1.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Gyenis
mesh_terms: D000818:Animals; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010750:Phosphoproteins; D020543:Proteome; D011494:Protein Kinases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
keywords: Kinome; Peptidyl–prolyl isomerase; Phosphoproteome; Pin1; Proline-directed kinase; Protein kinase