Pinning down signaling in the immune system: the role of the peptidyl-prolyl isomerase Pin1 in immune cell function.

Waisman Center for Developmental Disabilities, Department of Pathology and Laboratory Medicine and UW-Madison School of Medicine and Public Health, Madison, WI 53705, USA.
Critical Reviews in Immunology (Impact Factor: 3.89). 02/2008; 28(1):45-60. DOI: 10.1615/CritRevImmunol.v28.i1.30
Source: PubMed

ABSTRACT The peptidyl prolyl isomerase (PPIase) Pin1 has been recently implicated in cell cycle control and neuropathologies. There is now growing evidence that Pin1 plays an important role in the immune system and does so differentially from the related PPIases, cyclophilinA and FKBP. This review describes how Pin1 modulates cytokine expression by activated T cells and eosinophils and participates in T-cell and eosinophil apoptotic decisions both in vitro and in vivo. We highlight several possible immunologic diseases, including asthma, as well as organ transplant rejection, where anti-Pin1 therapeutics maybe of value.

Download full-text


Available from: Stephane Esnault, Sep 11, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pin1 is a peptidyl-prolyl isomerase (PPIase) that catalyzes the conversion of specific Pro-directed Ser/Thr phosphorylation motifs between the cis and trans conformations. It has been implicated in multiple aspects of cell cycle regulation and neural differentiation. In addition, Pin1 is involved in cellular processes related to a number of human pathologies, including cancer and Alzheimer's disease. More recent studies provided evidence for the participation of Pin1 in the regulation of immune cell functions and immune responses, independent of the activity of the related PPIases, cyclophilin A and FKBP, also known as immunophilins. In this review we focus on the role of Pin1 in the regulation of innate and adaptive immune system cell functions. Pin1 mediated isomerization of phosphoproteins represents a unique signaling mechanism that regulates normal immune functions and contributes to the development of immunopathologies. It can therefore serve as a useful diagnostic tool and a potential therapeutic target.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase (PPIase) that has the potential to add an additional level of regulation within protein kinase mediated signaling pathways. Furthermore, there is a mounting body of evidence implicating Pin1 in the emergence of pathological phenotypes in neurodegeneration and cancer through the isomerization of a wide variety of substrates at peptidyl-prolyl bonds where the residue preceding proline is a phosphorylated serine or threonine residue (i.e., pS/T-P motifs). A key step in this regulatory process is the interaction of Pin-1 with its substrates. This is a complex process since Pin1 is composed of two domains, the catalytic PPIase domain, and a type IV WW domain, both of which recognize pS/T-P motifs. The observation that the WW domain exhibits considerably higher binding affinity for pS/T-P motifs has led to predictions that the two domains may have distinct roles in mediating the actions of Pin1 on its substrates. To evaluate the participation of its individual domains in target binding, we performed GST pulldowns to monitor interactions between various forms of Pin1 and mitotic phospho-proteins that revealed two classes of Pin-1 interacting proteins, differing in their requirement for residues within the PPIase domain. From these observations, we consider models for Pin1-substrate interactions and the potential functions of the different classes of Pin1 interacting proteins. We also compare sequences that are recognized by Pin1 within its individual interaction partners to investigate the underlying basis for its different types of interactions.
    Frontiers in Physiology 02/2013; 4:18. DOI:10.3389/fphys.2013.00018 · 3.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Peptidylprolyl isomerases (PPIases) play essential roles in protein folding and are implicated in immune response and cell cycle control. Our previous proteomic analysis indicated that Bombyx mori PPIases may be involved in anti-Bombyx mori nucleopolyhedrovirus (BmNPV) response. To help investigate this mechanism, we cloned a B. mori PPIase gene PPIB and characterized it by bioinformatic and experimental analysis. We found that the B. mori PPIB gene contains 4 exons and its cDNA is about of 618 bp, encoding a protein of 205 amino acid residues (21474.41 Da) with an isoelectric point of 8.05. PPIB contains conserved and unique cyclophilin domain and belongs to cyclophilin superfamily. Its transcription could be detected by PCR in all the B. mori tissue samples, which is consistent with normal PPIase expression pattern and their essential roles. It is localized in cytoplasm revealed by fluorescence microscopy. We also successfully expressed this protein in E. coli and characterized it by SDS-PAGE and Mass Spectrometry. The cloned DNA sequence was submitted to GenBank (EU583493).
    AFRICAN JOURNAL OF BIOTECHNOLOGY 01/2010; 8(24):7116-7124. DOI:10.4314/ajb.v8i24.68806 · 0.57 Impact Factor

Similar Publications