Fyn mediates leptin actions in the thymus of rodents
Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects o...
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| creator | Girasol, Alessandra Albuquerque, Gabriela G Mansour, Eli Araújo, Eliana P Degasperi, Giovanna Denis, Raphael G Carvalheira, José B Saad, Mário J Velloso, Lício A |
| description | Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade.
Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression.
Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue. |
| doi_str_mv | 10.1371/journal.pone.0007707 |
| format | Article |
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Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression.
Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0007707</identifier><identifier>PMID: 19888448</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Activation ; Animal tissues ; Animals ; Antigens ; Apoptosis ; Cell Separation ; Cellular signal transduction ; Cytokines ; Diabetes and Endocrinology/Endocrinology ; Diabetes and Endocrinology/Obesity ; Experiments ; Fyn protein ; Gene Expression Regulation ; Genomes ; Immune system ; Immunology/Immunomodulation ; Immunomodulation ; Inhibition ; Insulin ; Internal medicine ; Janus kinase 2 ; Kinases ; Laboratories ; Leptin ; Leptin - physiology ; Ligands ; Lymphocytes ; Male ; Malnutrition ; Medicine ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Protein expression ; Protein-tyrosine kinase ; Proteins ; Proto-Oncogene Proteins c-fyn - metabolism ; Rats ; Rats, Wistar ; Receptors, Leptin - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rodentia ; Rodents ; Signal Transduction ; Signaling ; Thymus ; Thymus Gland - cytology ; Tyrosine</subject><ispartof>PloS one, 2009-11, Vol.4 (11), p.e7707-e7707</ispartof><rights>COPYRIGHT 2009 Public Library of Science</rights><rights>2009 Girasol et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Girasol et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c663t-a5e136c10888130ced1a0edb01a596146b44eb803b74bbde2c66af55af4d02083</citedby><cites>FETCH-LOGICAL-c663t-a5e136c10888130ced1a0edb01a596146b44eb803b74bbde2c66af55af4d02083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766049/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766049/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19888448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ferreira, Sérgio Teixeira</contributor><creatorcontrib>Girasol, Alessandra</creatorcontrib><creatorcontrib>Albuquerque, Gabriela G</creatorcontrib><creatorcontrib>Mansour, Eli</creatorcontrib><creatorcontrib>Araújo, Eliana P</creatorcontrib><creatorcontrib>Degasperi, Giovanna</creatorcontrib><creatorcontrib>Denis, Raphael G</creatorcontrib><creatorcontrib>Carvalheira, José B</creatorcontrib><creatorcontrib>Saad, Mário J</creatorcontrib><creatorcontrib>Velloso, Lício A</creatorcontrib><title>Fyn mediates leptin actions in the thymus of rodents</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade.
Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression.
Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Activation</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>Cell Separation</subject><subject>Cellular signal transduction</subject><subject>Cytokines</subject><subject>Diabetes and Endocrinology/Endocrinology</subject><subject>Diabetes and Endocrinology/Obesity</subject><subject>Experiments</subject><subject>Fyn protein</subject><subject>Gene Expression Regulation</subject><subject>Genomes</subject><subject>Immune system</subject><subject>Immunology/Immunomodulation</subject><subject>Immunomodulation</subject><subject>Inhibition</subject><subject>Insulin</subject><subject>Internal medicine</subject><subject>Janus kinase 2</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Leptin</subject><subject>Leptin - physiology</subject><subject>Ligands</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Malnutrition</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Protein expression</subject><subject>Protein-tyrosine kinase</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-fyn - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors, Leptin - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodentia</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Thymus</subject><subject>Thymus Gland - 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One</addtitle><date>2009-11-03</date><risdate>2009</risdate><volume>4</volume><issue>11</issue><spage>e7707</spage><epage>e7707</epage><pages>e7707-e7707</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade.
Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression.
Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>19888448</pmid><doi>10.1371/journal.pone.0007707</doi><tpages>e7707</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2009-11, Vol.4 (11), p.e7707-e7707 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1292244720 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | 1-Phosphatidylinositol 3-kinase Activation Animal tissues Animals Antigens Apoptosis Cell Separation Cellular signal transduction Cytokines Diabetes and Endocrinology/Endocrinology Diabetes and Endocrinology/Obesity Experiments Fyn protein Gene Expression Regulation Genomes Immune system Immunology/Immunomodulation Immunomodulation Inhibition Insulin Internal medicine Janus kinase 2 Kinases Laboratories Leptin Leptin - physiology Ligands Lymphocytes Male Malnutrition Medicine Mice Mice, Inbred C57BL Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Protein expression Protein-tyrosine kinase Proteins Proto-Oncogene Proteins c-fyn - metabolism Rats Rats, Wistar Receptors, Leptin - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodentia Rodents Signal Transduction Signaling Thymus Thymus Gland - cytology Tyrosine |
| title | Fyn mediates leptin actions in the thymus of rodents |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T01%3A30%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fyn%20mediates%20leptin%20actions%20in%20the%20thymus%20of%20rodents&rft.jtitle=PloS%20one&rft.au=Girasol,%20Alessandra&rft.date=2009-11-03&rft.volume=4&rft.issue=11&rft.spage=e7707&rft.epage=e7707&rft.pages=e7707-e7707&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0007707&rft_dat=%3Cgale_plos_%3EA472814354%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1292244720&rft_id=info:pmid/19888448&rft_galeid=A472814354&rft_doaj_id=oai_doaj_org_article_cb058041e12f41ee9c918a187483dc45&rfr_iscdi=true |