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Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) plays critical roles in neural development and is increasingly recognized as a major mediator of injury response in the nervous system. Cytokines and growth factors are known to phosphorylate STAT3 at tyrosine(705) with or withou...

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Autores principales: Zhou, Lihan, Too, Heng-Phon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124549/
https://www.ncbi.nlm.nih.gov/pubmed/21738764
http://dx.doi.org/10.1371/journal.pone.0021680
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author Zhou, Lihan
Too, Heng-Phon
author_facet Zhou, Lihan
Too, Heng-Phon
author_sort Zhou, Lihan
collection PubMed
description BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) plays critical roles in neural development and is increasingly recognized as a major mediator of injury response in the nervous system. Cytokines and growth factors are known to phosphorylate STAT3 at tyrosine(705) with or without the concomitant phosphorylation at serine(727), resulting in the nuclear localization of STAT3 and subsequent transcriptional activation of genes. Recent evidence suggests that STAT3 may control cell function via alternative mechanisms independent of its transcriptional activity. Currently, the involvement of STAT3 mono-phosphorylated at residue serine(727) (P-Ser-STAT3) in neurite outgrowth and the underlying mechanism is largely unknown. PRINCIPAL FINDINGS: In this study, we investigated the role of nerve growth factor (NGF) induced P-Ser-STAT3 in mediating neurite outgrowth. NGF induced the phosphorylation of residue serine(727) but not tyrosine(705) of STAT3 in PC12 and primary cortical neuronal cells. In PC12 cells, serine but not tyrosine dominant negative mutant of STAT3 was found to impair NGF induced neurite outgrowth. Unexpectedly, NGF induced P-Ser-STAT3 was localized to the mitochondria but not in the nucleus. Mitochondrial STAT3 was further found to be intimately involved in NGF induced neurite outgrowth and the production of reactive oxygen species (ROS). CONCLUSION: Taken together, the findings herein demonstrated a hitherto unrecognized novel transcription independent mechanism whereby the mitochondria localized P-Ser-STAT3 is involved in NGF induced neurite outgrowth.
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spelling pubmed-31245492011-07-07 Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth Zhou, Lihan Too, Heng-Phon PLoS One Research Article BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) plays critical roles in neural development and is increasingly recognized as a major mediator of injury response in the nervous system. Cytokines and growth factors are known to phosphorylate STAT3 at tyrosine(705) with or without the concomitant phosphorylation at serine(727), resulting in the nuclear localization of STAT3 and subsequent transcriptional activation of genes. Recent evidence suggests that STAT3 may control cell function via alternative mechanisms independent of its transcriptional activity. Currently, the involvement of STAT3 mono-phosphorylated at residue serine(727) (P-Ser-STAT3) in neurite outgrowth and the underlying mechanism is largely unknown. PRINCIPAL FINDINGS: In this study, we investigated the role of nerve growth factor (NGF) induced P-Ser-STAT3 in mediating neurite outgrowth. NGF induced the phosphorylation of residue serine(727) but not tyrosine(705) of STAT3 in PC12 and primary cortical neuronal cells. In PC12 cells, serine but not tyrosine dominant negative mutant of STAT3 was found to impair NGF induced neurite outgrowth. Unexpectedly, NGF induced P-Ser-STAT3 was localized to the mitochondria but not in the nucleus. Mitochondrial STAT3 was further found to be intimately involved in NGF induced neurite outgrowth and the production of reactive oxygen species (ROS). CONCLUSION: Taken together, the findings herein demonstrated a hitherto unrecognized novel transcription independent mechanism whereby the mitochondria localized P-Ser-STAT3 is involved in NGF induced neurite outgrowth. Public Library of Science 2011-06-27 /pmc/articles/PMC3124549/ /pubmed/21738764 http://dx.doi.org/10.1371/journal.pone.0021680 Text en Zhou, Too. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhou, Lihan
Too, Heng-Phon
Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth
title Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth
title_full Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth
title_fullStr Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth
title_full_unstemmed Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth
title_short Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth
title_sort mitochondrial localized stat3 is involved in ngf induced neurite outgrowth
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124549/
https://www.ncbi.nlm.nih.gov/pubmed/21738764
http://dx.doi.org/10.1371/journal.pone.0021680
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