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Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571201/ https://www.ncbi.nlm.nih.gov/pubmed/23407864 http://dx.doi.org/10.3389/fphys.2013.00018 |
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author | Innes, Brendan T. Bailey, Melanie L. Brandl, Christopher J. Shilton, Brian H. Litchfield, David W. |
author_facet | Innes, Brendan T. Bailey, Melanie L. Brandl, Christopher J. Shilton, Brian H. Litchfield, David W. |
author_sort | Innes, Brendan T. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3571201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-35712012013-02-13 Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding Innes, Brendan T. Bailey, Melanie L. Brandl, Christopher J. Shilton, Brian H. Litchfield, David W. Front Physiol Physiology 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 Media S.A. 2013-02-13 /pmc/articles/PMC3571201/ /pubmed/23407864 http://dx.doi.org/10.3389/fphys.2013.00018 Text en Copyright © 2013 Innes, Bailey, Brandl, Shilton and Litchfield. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Physiology Innes, Brendan T. Bailey, Melanie L. Brandl, Christopher J. Shilton, Brian H. Litchfield, David W. Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding |
title | Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding |
title_full | Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding |
title_fullStr | Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding |
title_full_unstemmed | Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding |
title_short | Non-catalytic participation of the Pin1 peptidyl-prolyl isomerase domain in target binding |
title_sort | non-catalytic participation of the pin1 peptidyl-prolyl isomerase domain in target binding |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571201/ https://www.ncbi.nlm.nih.gov/pubmed/23407864 http://dx.doi.org/10.3389/fphys.2013.00018 |
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