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The two faces of Janus kinases and their respective STATs in mammary gland development and cancer

Since its discovery as “just another kinase” more than twenty years ago, the family of JAK tyrosine kinases and their respective Signal Transducers and Activators of Transcription (STATs) has been a center of attention in the areas of signal transduction, development, and cancer. The subsequent desi...

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Autores principales: Wagner, Kay-Uwe, Schmidt, Jeffrey W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262999/
https://www.ncbi.nlm.nih.gov/pubmed/22279417
http://dx.doi.org/10.4103/1477-3163.90677
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author Wagner, Kay-Uwe
Schmidt, Jeffrey W.
author_facet Wagner, Kay-Uwe
Schmidt, Jeffrey W.
author_sort Wagner, Kay-Uwe
collection PubMed
description Since its discovery as “just another kinase” more than twenty years ago, the family of JAK tyrosine kinases and their respective Signal Transducers and Activators of Transcription (STATs) has been a center of attention in the areas of signal transduction, development, and cancer. The subsequent designation of JAKs as Janus kinases after the mythical two-faced Roman God of the doorways accurately portrays the analogous and sometimes contrasting molecular and biological characteristics of these tyrosine kinases. The two “faces” of JAKs are their structurally similar kinase and pseudo-kinase domains. As essential parts of various transmembrane receptor complexes, these tyrosine kinases function at cellular gateways and relay signals from growth factors to their respective intracellular targets. The multifaceted nature of JAKs becomes evident from their ability to activate specific STATs during distinct phases of normal mammary gland development. Studies in breast cancer cells and genetically engineered mouse models also show that JAK/STAT signaling possesses a "two-faced" role during breast cancer initiation and progression. This review will highlight recent findings about important biological functions of JAKs and STATs during normal mammogenesis, with particular emphasis on the Jak2/Stat5 pathway as well as Jak1/2/Stat3 signaling complexes. In addition, we will discuss how the importance of these signaling networks changes during carcinogenesis. With JAK inhibitors currently under development to treat myeloproliferative disorders, determining the essential functions of JAKs at particular stages of disease initiation and progression is of critical importance to predict the efficacy of these agents for targeted therapies against breast cancer.
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spelling pubmed-32629992012-01-25 The two faces of Janus kinases and their respective STATs in mammary gland development and cancer Wagner, Kay-Uwe Schmidt, Jeffrey W. J Carcinog Review Article Since its discovery as “just another kinase” more than twenty years ago, the family of JAK tyrosine kinases and their respective Signal Transducers and Activators of Transcription (STATs) has been a center of attention in the areas of signal transduction, development, and cancer. The subsequent designation of JAKs as Janus kinases after the mythical two-faced Roman God of the doorways accurately portrays the analogous and sometimes contrasting molecular and biological characteristics of these tyrosine kinases. The two “faces” of JAKs are their structurally similar kinase and pseudo-kinase domains. As essential parts of various transmembrane receptor complexes, these tyrosine kinases function at cellular gateways and relay signals from growth factors to their respective intracellular targets. The multifaceted nature of JAKs becomes evident from their ability to activate specific STATs during distinct phases of normal mammary gland development. Studies in breast cancer cells and genetically engineered mouse models also show that JAK/STAT signaling possesses a "two-faced" role during breast cancer initiation and progression. This review will highlight recent findings about important biological functions of JAKs and STATs during normal mammogenesis, with particular emphasis on the Jak2/Stat5 pathway as well as Jak1/2/Stat3 signaling complexes. In addition, we will discuss how the importance of these signaling networks changes during carcinogenesis. With JAK inhibitors currently under development to treat myeloproliferative disorders, determining the essential functions of JAKs at particular stages of disease initiation and progression is of critical importance to predict the efficacy of these agents for targeted therapies against breast cancer. Medknow Publications & Media Pvt Ltd 2011-12-08 /pmc/articles/PMC3262999/ /pubmed/22279417 http://dx.doi.org/10.4103/1477-3163.90677 Text en © 2011 Wagner http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Wagner, Kay-Uwe
Schmidt, Jeffrey W.
The two faces of Janus kinases and their respective STATs in mammary gland development and cancer
title The two faces of Janus kinases and their respective STATs in mammary gland development and cancer
title_full The two faces of Janus kinases and their respective STATs in mammary gland development and cancer
title_fullStr The two faces of Janus kinases and their respective STATs in mammary gland development and cancer
title_full_unstemmed The two faces of Janus kinases and their respective STATs in mammary gland development and cancer
title_short The two faces of Janus kinases and their respective STATs in mammary gland development and cancer
title_sort two faces of janus kinases and their respective stats in mammary gland development and cancer
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262999/
https://www.ncbi.nlm.nih.gov/pubmed/22279417
http://dx.doi.org/10.4103/1477-3163.90677
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