Pin1: Intimate involvement with the regulatory protein kinase networks in the global phosphorylation landscape

• Published in: Biochimica et biophysica acta Vol. 1850; no. 10; pp. 2077 - 2086
• Main Authors: Litchfield, David W., Shilton, Brian H., Brandl, Christopher J., Gyenis, Laszlo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2015
• Subjects: Animals; catalysts; drugs; functional properties; Humans; Kinome; NIMA-Interacting Peptidylprolyl Isomerase; peptidylprolyl isomerase; Peptidylprolyl Isomerase - genetics; Peptidylprolyl Isomerase - metabolism; Peptidyl–prolyl isomerase; Phosphoproteins - metabolism; Phosphoproteome; Phosphorylation - physiology; Pin1; Proline-directed kinase; Protein kinase; protein kinases; Protein Kinases - genetics; Protein Kinases - metabolism; protein phosphorylation; protein-protein interactions; proteome; Proteome - genetics; Proteome - metabolism; regulatory proteins; Kinome; Pin1; Peptidyl–prolyl isomerase; Phosphoproteome; Protein kinase; Proline-directed kinase
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2015.02.018

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. 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. 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. 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. [Display omitted] •Pin1 has complex interactions with the kinome and proline-directed phosphoproteome.•Several proline-directed protein kinases generate Pin1 recognition motifs.•Proline-directed sites typically represent 1/4th to 1/3rd of the phosphoproteome.•Pin1 exerts positive or negative effects on several distinct protein kinases.•Pin1 is regulated positively and negatively by phosphorylation in cells.