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Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors

Identifieur interne : 000162 ( Pmc/Curation ); précédent : 000161; suivant : 000163

Application of computational approaches to study signalling networks of nuclear and Tyrosine kinase receptors

Auteurs : Mouna Choura [Tunisie] ; Ahmed Rebaï [Tunisie]

Source :

RBID : PMC:2964540

Abstract

Background

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.

Results

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 http://www.bioinfo-cbs.org/NR-RTK/

Conclusions

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.

Reviewers

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

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PMC:2964540

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<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>
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<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>
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<journal-title>Biology Direct</journal-title>
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<article-id pub-id-type="pmc">2964540</article-id>
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<article-id pub-id-type="doi">10.1186/1745-6150-5-58</article-id>
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</title-group>
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<name>
<surname>Choura</surname>
<given-names>Mouna</given-names>
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<email>mouna.choura@cbs.rnrt.tn</email>
</contrib>
<contrib contrib-type="author" corresp="yes" id="A2">
<name>
<surname>Rebaï</surname>
<given-names>Ahmed</given-names>
</name>
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<email>ahmed.rebai@cbs.rnrt.tn</email>
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<aff id="I1">
<label>1</label>
Molecular and Cellular Diagnosis Processes, Centre of Biotechnology of Sfax, Route Sidi Mansour, Sfax, Tunisia</aff>
<pub-date pub-type="collection">
<year>2010</year>
</pub-date>
<pub-date pub-type="epub">
<day>11</day>
<month>10</month>
<year>2010</year>
</pub-date>
<volume>5</volume>
<fpage>58</fpage>
<lpage>58</lpage>
<history>
<date date-type="received">
<day>27</day>
<month>9</month>
<year>2010</year>
</date>
<date date-type="accepted">
<day>11</day>
<month>10</month>
<year>2010</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright ©2010 Choura and Rebaï; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2010</copyright-year>
<copyright-holder>Choura and Rebaï; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0">
<license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://www.biology-direct.com/content/5/1/58"></self-uri>
<abstract>
<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>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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