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Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways
Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been shown to regulate diverse cellular functions such as cell size, proliferation, and migration in vitro. However, the function of FIP200 in vivo has not been investigated. We show that targeted deletion of FIP200 in the mouse...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064504/ https://www.ncbi.nlm.nih.gov/pubmed/17015619 http://dx.doi.org/10.1083/jcb.200604129 |
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author | Gan, Boyi Peng, Xu Nagy, Tamas Alcaraz, Ana Gu, Hua Guan, Jun-Lin |
author_facet | Gan, Boyi Peng, Xu Nagy, Tamas Alcaraz, Ana Gu, Hua Guan, Jun-Lin |
author_sort | Gan, Boyi |
collection | PubMed |
description | Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been shown to regulate diverse cellular functions such as cell size, proliferation, and migration in vitro. However, the function of FIP200 in vivo has not been investigated. We show that targeted deletion of FIP200 in the mouse led to embryonic death at mid/late gestation associated with heart failure and liver degeneration. We found that FIP200 knockout (KO) embryos show reduced S6 kinase activation and cell size as a result of increased tuberous sclerosis complex function. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver. Consistent with this, FIP200 KO mouse embryo fibroblasts and liver cells showed increased apoptosis and reduced c-Jun N-terminal kinase phosphorylation in response to tumor necrosis factor (TNF) α stimulation, which might be mediated by FIP200 interaction with apoptosis signal–regulating kinase 1 (ASK1) and TNF receptor–associated factor 2 (TRAF2), regulation of TRAF2–ASK1 interaction, and ASK1 phosphorylation. Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis. |
format | Text |
id | pubmed-2064504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20645042007-11-29 Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways Gan, Boyi Peng, Xu Nagy, Tamas Alcaraz, Ana Gu, Hua Guan, Jun-Lin J Cell Biol Research Articles Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been shown to regulate diverse cellular functions such as cell size, proliferation, and migration in vitro. However, the function of FIP200 in vivo has not been investigated. We show that targeted deletion of FIP200 in the mouse led to embryonic death at mid/late gestation associated with heart failure and liver degeneration. We found that FIP200 knockout (KO) embryos show reduced S6 kinase activation and cell size as a result of increased tuberous sclerosis complex function. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver. Consistent with this, FIP200 KO mouse embryo fibroblasts and liver cells showed increased apoptosis and reduced c-Jun N-terminal kinase phosphorylation in response to tumor necrosis factor (TNF) α stimulation, which might be mediated by FIP200 interaction with apoptosis signal–regulating kinase 1 (ASK1) and TNF receptor–associated factor 2 (TRAF2), regulation of TRAF2–ASK1 interaction, and ASK1 phosphorylation. Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis. The Rockefeller University Press 2006-10-09 /pmc/articles/PMC2064504/ /pubmed/17015619 http://dx.doi.org/10.1083/jcb.200604129 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Gan, Boyi Peng, Xu Nagy, Tamas Alcaraz, Ana Gu, Hua Guan, Jun-Lin Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways |
title | Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways |
title_full | Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways |
title_fullStr | Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways |
title_full_unstemmed | Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways |
title_short | Role of FIP200 in cardiac and liver development and its regulation of TNFα and TSC–mTOR signaling pathways |
title_sort | role of fip200 in cardiac and liver development and its regulation of tnfα and tsc–mtor signaling pathways |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064504/ https://www.ncbi.nlm.nih.gov/pubmed/17015619 http://dx.doi.org/10.1083/jcb.200604129 |
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