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Novel Role of Src in Priming Pyk2 Phosphorylation
Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) family of non-receptor tyrosine kinases and plays an important role in diverse cellular events downstream of the integrin-family of receptors, including cell migration, proliferation and survival. Here, we have iden...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750869/ https://www.ncbi.nlm.nih.gov/pubmed/26866924 http://dx.doi.org/10.1371/journal.pone.0149231 |
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author | Zhao, Ming Finlay, Darren Zharkikh, Irina Vuori, Kristiina |
author_facet | Zhao, Ming Finlay, Darren Zharkikh, Irina Vuori, Kristiina |
author_sort | Zhao, Ming |
collection | PubMed |
description | Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) family of non-receptor tyrosine kinases and plays an important role in diverse cellular events downstream of the integrin-family of receptors, including cell migration, proliferation and survival. Here, we have identified a novel role for Src kinase in priming Pyk2 phosphorylation and subsequent activation upon cell attachment on the integrin-ligand fibronectin. By using complementary methods, we show that Src activity is indispensable for the initial Pyk2 phosphorylation on the Y402 site observed in response to cell attachment. In contrast, the initial fibronectin-induced autophosphorylation of FAK in the homologous Y397 site occurs in a Src-independent manner. We demonstrate that the SH2-domain of Src is required for Src binding to Pyk2 and for Pyk2 phosphorylation at sites Y402 and Y579. Moreover, Y402 phosphorylation is a prerequisite for the subsequent Y579 phosphorylation. While this initial phosphorylation of Pyk2 by Src is independent of Pyk2 kinase activity, subsequent autophosphorylation of Pyk2 in trans is required for full Pyk2 phosphorylation and activation. Collectively, our studies reveal a novel function of Src in priming Pyk2 (but not FAK) phosphorylation and subsequent activation downstream of integrins, and shed light on the signaling events that regulate the function of Pyk2. |
format | Online Article Text |
id | pubmed-4750869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47508692016-02-26 Novel Role of Src in Priming Pyk2 Phosphorylation Zhao, Ming Finlay, Darren Zharkikh, Irina Vuori, Kristiina PLoS One Research Article Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) family of non-receptor tyrosine kinases and plays an important role in diverse cellular events downstream of the integrin-family of receptors, including cell migration, proliferation and survival. Here, we have identified a novel role for Src kinase in priming Pyk2 phosphorylation and subsequent activation upon cell attachment on the integrin-ligand fibronectin. By using complementary methods, we show that Src activity is indispensable for the initial Pyk2 phosphorylation on the Y402 site observed in response to cell attachment. In contrast, the initial fibronectin-induced autophosphorylation of FAK in the homologous Y397 site occurs in a Src-independent manner. We demonstrate that the SH2-domain of Src is required for Src binding to Pyk2 and for Pyk2 phosphorylation at sites Y402 and Y579. Moreover, Y402 phosphorylation is a prerequisite for the subsequent Y579 phosphorylation. While this initial phosphorylation of Pyk2 by Src is independent of Pyk2 kinase activity, subsequent autophosphorylation of Pyk2 in trans is required for full Pyk2 phosphorylation and activation. Collectively, our studies reveal a novel function of Src in priming Pyk2 (but not FAK) phosphorylation and subsequent activation downstream of integrins, and shed light on the signaling events that regulate the function of Pyk2. Public Library of Science 2016-02-11 /pmc/articles/PMC4750869/ /pubmed/26866924 http://dx.doi.org/10.1371/journal.pone.0149231 Text en © 2016 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zhao, Ming Finlay, Darren Zharkikh, Irina Vuori, Kristiina Novel Role of Src in Priming Pyk2 Phosphorylation |
title | Novel Role of Src in Priming Pyk2 Phosphorylation |
title_full | Novel Role of Src in Priming Pyk2 Phosphorylation |
title_fullStr | Novel Role of Src in Priming Pyk2 Phosphorylation |
title_full_unstemmed | Novel Role of Src in Priming Pyk2 Phosphorylation |
title_short | Novel Role of Src in Priming Pyk2 Phosphorylation |
title_sort | novel role of src in priming pyk2 phosphorylation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750869/ https://www.ncbi.nlm.nih.gov/pubmed/26866924 http://dx.doi.org/10.1371/journal.pone.0149231 |
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