Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors
Identifieur interne : 000114 ( Main/Exploration ); précédent : 000113; suivant : 000115Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors
Auteurs : Mouna Choura [Tunisie] ; Ahmed Rebaï [Tunisie]Source :
- Biology Direct [ 1745-6150 ] ; 2010.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Transduction du signal.
- métabolisme : Récepteurs cytoplasmiques et nucléaires, Récepteurs à activité tyrosine kinase.
- méthodes : Biologie informatique.
- physiologie : Transduction du signal.
- Humains.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Receptor Protein-Tyrosine Kinases, Receptors, Cytoplasmic and Nuclear.
- genetics : Signal Transduction.
- methods : Computational Biology.
- physiology : Signal Transduction.
- Humans.
Abstract
Nuclear receptors (NRs) and Receptor tyrosine kinases (RTKs) are essential proteins in many cellular processes and sequence variations in their genes have been reported to be involved in many diseases including cancer. Although crosstalk between RTK and NR signalling and their contribution to the development of endocrine regulated cancers have been areas of intense investigation, the direct coupling of their signalling pathways remains elusive. In our understanding of the role and function of nuclear receptors on the cell membrane the interactions between nuclear receptors and tyrosine kinase receptors deserve further attention.
We constructed a human signalling network containing nuclear receptors and tyrosine kinase receptors that identified a network topology involving eleven highly connected hubs.
We further developed an integrated knowledge database, denominated NR-RTK database dedicated to human RTKs and NRs and their vertebrate orthologs and their interactions. These interactions were inferred using computational tools and those supported by literature evidence are indicated. NR-RTK database contains links to other relevant resources and includes data on receptor ligands. It aims to provide a comprehensive interaction map that identifies complex dynamics and potential crosstalk involved.
Availability: NR-RTK database is accessible at
We infer that the NR-RTK interaction network is scale-free topology. We also uncovered the key receptors mediating the signal transduction between these two types of receptors. Furthermore, NR-RTK database is expected to be useful for researchers working on various aspects of the molecular basis of signal transduction by RTKs and NRs.
This article was reviewed by Professor Paul Harrison (nominated by Dr. Mark Gerstein), Dr. Arcady Mushegian and Dr. Anthony Almudevar.
Url:
DOI: 10.1186/1745-6150-5-58
PubMed: 20937105
PubMed Central: 2964540
Affiliations:
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Le document en format XML
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id="I1">Molecular and Cellular Diagnosis Processes, Centre of Biotechnology of Sfax, Route Sidi Mansour, Sfax, Tunisia</nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>Molecular and Cellular Diagnosis Processes, Centre of Biotechnology of Sfax, Route Sidi Mansour, Sfax</wicri:regionArea></affiliation></author><author><name sortKey="Rebai, Ahmed" sort="Rebai, Ahmed" uniqKey="Rebai A" first="Ahmed" last="Rebaï">Ahmed Rebaï</name><affiliation wicri:level="1"><nlm:aff id="I1">Molecular and Cellular Diagnosis Processes, Centre of Biotechnology of Sfax, Route Sidi Mansour, Sfax, Tunisia</nlm:aff><country xml:lang="fr">Tunisie</country><wicri:regionArea>Molecular and Cellular Diagnosis Processes, Centre of Biotechnology of Sfax, Route Sidi Mansour, Sfax</wicri:regionArea></affiliation></author></analytic><series><title level="j">Biology Direct</title><idno type="eISSN">1745-6150</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Computational Biology (methods)</term><term>Humans (MeSH)</term><term>Receptor Protein-Tyrosine Kinases (metabolism)</term><term>Receptors, Cytoplasmic and Nuclear (metabolism)</term><term>Signal Transduction (genetics)</term><term>Signal Transduction (physiology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Biologie informatique (méthodes)</term><term>Humains (MeSH)</term><term>Récepteurs cytoplasmiques et nucléaires (métabolisme)</term><term>Récepteurs à activité tyrosine kinase (métabolisme)</term><term>Transduction du signal (génétique)</term><term>Transduction du signal (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Receptor Protein-Tyrosine Kinases</term><term>Receptors, Cytoplasmic and Nuclear</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Computational Biology</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Récepteurs cytoplasmiques et nucléaires</term><term>Récepteurs à activité tyrosine kinase</term></keywords><keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Biologie informatique</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Nuclear receptors (NRs) and Receptor tyrosine kinases (RTKs) are essential proteins in many cellular processes and sequence variations in their genes have been reported to be involved in many diseases including cancer. Although crosstalk between RTK and NR signalling and their contribution to the development of endocrine regulated cancers have been areas of intense investigation, the direct coupling of their signalling pathways remains elusive. In our understanding of the role and function of nuclear receptors on the cell membrane the interactions between nuclear receptors and tyrosine kinase receptors deserve further attention.</p></sec><sec><title>Results</title><p>We constructed a human signalling network containing nuclear receptors and tyrosine kinase receptors that identified a network topology involving eleven highly connected hubs.</p><p>We further developed an integrated knowledge database, denominated NR-RTK database dedicated to human RTKs and NRs and their vertebrate orthologs and their interactions. These interactions were inferred using computational tools and those supported by literature evidence are indicated. NR-RTK database contains links to other relevant resources and includes data on receptor ligands. It aims to provide a comprehensive interaction map that identifies complex dynamics and potential crosstalk involved.</p><p>Availability: NR-RTK database is accessible at <ext-link ext-link-type="uri" xlink:href="http://www.bioinfo-cbs.org/NR-RTK/">http://www.bioinfo-cbs.org/NR-RTK/</ext-link></p></sec><sec><title>Conclusions</title><p>We infer that the NR-RTK interaction network is scale-free topology. We also uncovered the key receptors mediating the signal transduction between these two types of receptors. Furthermore, NR-RTK database is expected to be useful for researchers working on various aspects of the molecular basis of signal transduction by RTKs and NRs.</p></sec><sec><title>Reviewers</title><p>This article was reviewed by Professor Paul Harrison (nominated by Dr. Mark Gerstein), Dr. Arcady Mushegian and Dr. Anthony Almudevar.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bookout, Al" uniqKey="Bookout A">AL Bookout</name></author><author><name sortKey="Jeong, Y" uniqKey="Jeong Y">Y Jeong</name></author><author><name sortKey="Downes, M" uniqKey="Downes M">M Downes</name></author><author><name sortKey="Yu, Rt" uniqKey="Yu R">RT Yu</name></author><author><name sortKey="Evans, Rm" uniqKey="Evans R">RM Evans</name></author><author><name sortKey="Mangelsdorf, Dj" uniqKey="Mangelsdorf D">DJ Mangelsdorf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shulman, Ai" uniqKey="Shulman A">AI 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