Lens differentiation is controlled by the balance between PDGF and FGF signaling
How multiple receptor tyrosine kinases coordinate cell fate determination is yet to be elucidated. We show here that the receptor for platelet-derived growth factor (PDGF) signaling recruits the p85 subunit of Phosphoinositide 3-kinase (PI3K) to regulate mammalian lens development. Activation of PI3...
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| Veröffentlicht in: | PLoS biology 2019-02, Vol.17 (2), p.e3000133-e3000133 |
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| creator | Li, Hongge Mao, Yingyu Bouaziz, Michael Yu, Honglian Qu, Xiuxia Wang, Fen Feng, Gen-Sheng Shawber, Carrie Zhang, Xin |
| description | How multiple receptor tyrosine kinases coordinate cell fate determination is yet to be elucidated. We show here that the receptor for platelet-derived growth factor (PDGF) signaling recruits the p85 subunit of Phosphoinositide 3-kinase (PI3K) to regulate mammalian lens development. Activation of PI3K signaling not only prevents B-cell lymphoma 2 (BCL2)-Associated X (Bax)- and BCL2 Antagonist/Killer (Bak)-mediated apoptosis but also promotes Notch signaling to prevent premature cell differentiation. Reducing PI3K activity destabilizes the Notch intracellular domain, while the constitutive activation of Notch reverses the PI3K deficiency phenotype. In contrast, fibroblast growth factor receptors (FGFRs) recruit Fibroblast Growth Factor Receptor Substrate 2 (Frs2) and Rous sarcoma oncogene (Src) Homology Phosphatase 2 (Shp2) to activate Mitogen-Activated Protein Kinase (MAPK) signaling, which induces the Notch ligand Jagged 1 (Jag1) and promotes cell differentiation. Inactivation of Shp2 restored the proper timing of differentiation in the p85 mutant lens, demonstrating the antagonistic interaction between FGF-induced MAPK and PDGF-induced PI3K signaling. By selective activation of PI3K and MAPK, PDGF and FGF cooperate with and oppose each other to balance progenitor cell maintenance and differentiation. |
| doi_str_mv | 10.1371/journal.pbio.3000133 |
| format | Article |
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We show here that the receptor for platelet-derived growth factor (PDGF) signaling recruits the p85 subunit of Phosphoinositide 3-kinase (PI3K) to regulate mammalian lens development. Activation of PI3K signaling not only prevents B-cell lymphoma 2 (BCL2)-Associated X (Bax)- and BCL2 Antagonist/Killer (Bak)-mediated apoptosis but also promotes Notch signaling to prevent premature cell differentiation. Reducing PI3K activity destabilizes the Notch intracellular domain, while the constitutive activation of Notch reverses the PI3K deficiency phenotype. In contrast, fibroblast growth factor receptors (FGFRs) recruit Fibroblast Growth Factor Receptor Substrate 2 (Frs2) and Rous sarcoma oncogene (Src) Homology Phosphatase 2 (Shp2) to activate Mitogen-Activated Protein Kinase (MAPK) signaling, which induces the Notch ligand Jagged 1 (Jag1) and promotes cell differentiation. Inactivation of Shp2 restored the proper timing of differentiation in the p85 mutant lens, demonstrating the antagonistic interaction between FGF-induced MAPK and PDGF-induced PI3K signaling. By selective activation of PI3K and MAPK, PDGF and FGF cooperate with and oppose each other to balance progenitor cell maintenance and differentiation.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.3000133</identifier><identifier>PMID: 30716082</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Activation ; Animals ; Apoptosis ; B-cell lymphoma ; Bax protein ; bcl-2 Homologous Antagonist-Killer Protein - genetics ; bcl-2-Associated X Protein - genetics ; Biology ; Biology and Life Sciences ; Cell cycle ; Cell Differentiation ; Cell fate ; Cell growth ; Cell Survival ; Cells (biology) ; Deactivation ; Departments ; Differentiation (biology) ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Fibroblast growth factor receptors ; Fibroblast growth factors ; Fibroblast Growth Factors - metabolism ; Fibroblasts ; Genes ; Growth factor receptors ; Growth factors ; Homology ; Inactivation ; Kinases ; Lens, Crystalline - cytology ; Lens, Crystalline - embryology ; Lens, Crystalline - metabolism ; Lenses ; Ligands ; Lymphocytes B ; Lymphoma ; Mammals ; MAP kinase ; MAP Kinase Signaling System ; Medicine and Health Sciences ; Mice ; Mutation - genetics ; Observations ; Pathology ; Phenotypes ; Phosphatidylinositol 3-Kinases - metabolism ; Physiological aspects ; Platelet-derived growth factor ; Platelet-Derived Growth Factor - metabolism ; Progenitor cells ; Protein Domains ; Protein kinase ; Protein Stability ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Receptor, Platelet-Derived Growth Factor alpha - metabolism ; Receptors ; Receptors, Notch - chemistry ; Receptors, Notch - metabolism ; Rous sarcoma ; Sarcoma ; Signal Transduction ; Signaling ; Substrates ; Tyrosine</subject><ispartof>PLoS biology, 2019-02, Vol.17 (2), p.e3000133-e3000133</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (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>2019 Li et al 2019 Li et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c761t-9f50d444acdcc0a2076466a1726f8fc6218c8fd153c75bc5a43220c7be1c95d3</citedby><cites>FETCH-LOGICAL-c761t-9f50d444acdcc0a2076466a1726f8fc6218c8fd153c75bc5a43220c7be1c95d3</cites><orcidid>0000-0001-5555-0825 ; 0000-0001-5182-7401</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375662/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375662/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30716082$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bronner, Marianne E.</contributor><creatorcontrib>Li, Hongge</creatorcontrib><creatorcontrib>Mao, Yingyu</creatorcontrib><creatorcontrib>Bouaziz, Michael</creatorcontrib><creatorcontrib>Yu, Honglian</creatorcontrib><creatorcontrib>Qu, Xiuxia</creatorcontrib><creatorcontrib>Wang, Fen</creatorcontrib><creatorcontrib>Feng, Gen-Sheng</creatorcontrib><creatorcontrib>Shawber, Carrie</creatorcontrib><creatorcontrib>Zhang, Xin</creatorcontrib><title>Lens differentiation is controlled by the balance between PDGF and FGF signaling</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>How multiple receptor tyrosine kinases coordinate cell fate determination is yet to be elucidated. We show here that the receptor for platelet-derived growth factor (PDGF) signaling recruits the p85 subunit of Phosphoinositide 3-kinase (PI3K) to regulate mammalian lens development. Activation of PI3K signaling not only prevents B-cell lymphoma 2 (BCL2)-Associated X (Bax)- and BCL2 Antagonist/Killer (Bak)-mediated apoptosis but also promotes Notch signaling to prevent premature cell differentiation. Reducing PI3K activity destabilizes the Notch intracellular domain, while the constitutive activation of Notch reverses the PI3K deficiency phenotype. In contrast, fibroblast growth factor receptors (FGFRs) recruit Fibroblast Growth Factor Receptor Substrate 2 (Frs2) and Rous sarcoma oncogene (Src) Homology Phosphatase 2 (Shp2) to activate Mitogen-Activated Protein Kinase (MAPK) signaling, which induces the Notch ligand Jagged 1 (Jag1) and promotes cell differentiation. Inactivation of Shp2 restored the proper timing of differentiation in the p85 mutant lens, demonstrating the antagonistic interaction between FGF-induced MAPK and PDGF-induced PI3K signaling. By selective activation of PI3K and MAPK, PDGF and FGF cooperate with and oppose each other to balance progenitor cell maintenance and differentiation.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Activation</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>B-cell lymphoma</subject><subject>Bax protein</subject><subject>bcl-2 Homologous Antagonist-Killer Protein - genetics</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Cell cycle</subject><subject>Cell Differentiation</subject><subject>Cell fate</subject><subject>Cell growth</subject><subject>Cell Survival</subject><subject>Cells (biology)</subject><subject>Deactivation</subject><subject>Departments</subject><subject>Differentiation (biology)</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>Fibroblast growth factor receptors</subject><subject>Fibroblast growth factors</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Fibroblasts</subject><subject>Genes</subject><subject>Growth factor receptors</subject><subject>Growth factors</subject><subject>Homology</subject><subject>Inactivation</subject><subject>Kinases</subject><subject>Lens, Crystalline - cytology</subject><subject>Lens, Crystalline - embryology</subject><subject>Lens, Crystalline - metabolism</subject><subject>Lenses</subject><subject>Ligands</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Mammals</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mutation - genetics</subject><subject>Observations</subject><subject>Pathology</subject><subject>Phenotypes</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Physiological aspects</subject><subject>Platelet-derived growth factor</subject><subject>Platelet-Derived Growth Factor - metabolism</subject><subject>Progenitor cells</subject><subject>Protein Domains</subject><subject>Protein kinase</subject><subject>Protein Stability</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - metabolism</subject><subject>Receptors</subject><subject>Receptors, Notch - chemistry</subject><subject>Receptors, Notch - metabolism</subject><subject>Rous sarcoma</subject><subject>Sarcoma</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Substrates</subject><subject>Tyrosine</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqVks1uEzEUhUcIREvhDRCMxKYsEvzvmQ1S1ZISKaIVVGwtj309dTQZp_YE6NvjkGnVoC5AXlzL_u6xfXyK4jVGU0wl_rAMm9jrbrpufJhShBCm9ElxiDnjE1lV_OmD-UHxIqUlQoTUpHpeHFAksUAVOSwuF9Cn0nrnIEI_eD340Jc-lSb0QwxdB7ZsbsvhGspGd7o3ucLwE6AvL8_OZ6XubTnLNfk2X8b37cvimdNdgldjPSquZp-uTj9PFhfn89OTxcRIgYdJ7TiyjDFtrDFIEyQFE0JjSYSrnBEEV6ZyFnNqJG8M14wSgoxsAJuaW3pUvN3JrruQ1OhFUoSwuuZ1jVEm5jvCBr1U6-hXOt6qoL36sxBiq3QcvOlAAadaWwAna8ec1VVjuSZGaGEqgQVkrY_jaZtmBdZkp6Lu9kT3d3p_rdrwQwkquRAkCxyPAjHcbCANauWTgS47CmGT741lzRniAmf03V_o468bqVbnB_jehXyu2YqqEy4lqRDlLFPTR6g8LKx8_mFwPq_vNbzfa9imAH4Nrd6kpObfvv4H--Xf2Yvv-yzbsSaGlCK4e58xUtvo3xmittFXY_Rz25uHf3TfdJd1-hvy5_2m</recordid><startdate>20190204</startdate><enddate>20190204</enddate><creator>Li, Hongge</creator><creator>Mao, Yingyu</creator><creator>Bouaziz, Michael</creator><creator>Yu, Honglian</creator><creator>Qu, Xiuxia</creator><creator>Wang, Fen</creator><creator>Feng, Gen-Sheng</creator><creator>Shawber, Carrie</creator><creator>Zhang, Xin</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PATMY</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope><orcidid>https://orcid.org/0000-0001-5555-0825</orcidid><orcidid>https://orcid.org/0000-0001-5182-7401</orcidid></search><sort><creationdate>20190204</creationdate><title>Lens differentiation is controlled by the balance between PDGF and FGF signaling</title><author>Li, Hongge ; Mao, Yingyu ; Bouaziz, Michael ; Yu, Honglian ; Qu, Xiuxia ; Wang, Fen ; Feng, Gen-Sheng ; Shawber, Carrie ; Zhang, Xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c761t-9f50d444acdcc0a2076466a1726f8fc6218c8fd153c75bc5a43220c7be1c95d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Activation</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>B-cell lymphoma</topic><topic>Bax protein</topic><topic>bcl-2 Homologous Antagonist-Killer Protein - genetics</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Cell cycle</topic><topic>Cell Differentiation</topic><topic>Cell fate</topic><topic>Cell growth</topic><topic>Cell Survival</topic><topic>Cells (biology)</topic><topic>Deactivation</topic><topic>Departments</topic><topic>Differentiation (biology)</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>Fibroblast growth factor receptors</topic><topic>Fibroblast growth factors</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Fibroblasts</topic><topic>Genes</topic><topic>Growth factor receptors</topic><topic>Growth factors</topic><topic>Homology</topic><topic>Inactivation</topic><topic>Kinases</topic><topic>Lens, Crystalline - cytology</topic><topic>Lens, Crystalline - embryology</topic><topic>Lens, Crystalline - metabolism</topic><topic>Lenses</topic><topic>Ligands</topic><topic>Lymphocytes B</topic><topic>Lymphoma</topic><topic>Mammals</topic><topic>MAP kinase</topic><topic>MAP Kinase Signaling System</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mutation - genetics</topic><topic>Observations</topic><topic>Pathology</topic><topic>Phenotypes</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Physiological aspects</topic><topic>Platelet-derived growth factor</topic><topic>Platelet-Derived Growth Factor - metabolism</topic><topic>Progenitor cells</topic><topic>Protein Domains</topic><topic>Protein kinase</topic><topic>Protein Stability</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptor, Platelet-Derived Growth Factor alpha - metabolism</topic><topic>Receptors</topic><topic>Receptors, Notch - chemistry</topic><topic>Receptors, Notch - metabolism</topic><topic>Rous sarcoma</topic><topic>Sarcoma</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Substrates</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Hongge</creatorcontrib><creatorcontrib>Mao, Yingyu</creatorcontrib><creatorcontrib>Bouaziz, Michael</creatorcontrib><creatorcontrib>Yu, Honglian</creatorcontrib><creatorcontrib>Qu, Xiuxia</creatorcontrib><creatorcontrib>Wang, Fen</creatorcontrib><creatorcontrib>Feng, Gen-Sheng</creatorcontrib><creatorcontrib>Shawber, Carrie</creatorcontrib><creatorcontrib>Zhang, Xin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Hongge</au><au>Mao, Yingyu</au><au>Bouaziz, Michael</au><au>Yu, Honglian</au><au>Qu, Xiuxia</au><au>Wang, Fen</au><au>Feng, Gen-Sheng</au><au>Shawber, Carrie</au><au>Zhang, Xin</au><au>Bronner, Marianne E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lens differentiation is controlled by the balance between PDGF and FGF signaling</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2019-02-04</date><risdate>2019</risdate><volume>17</volume><issue>2</issue><spage>e3000133</spage><epage>e3000133</epage><pages>e3000133-e3000133</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>How multiple receptor tyrosine kinases coordinate cell fate determination is yet to be elucidated. We show here that the receptor for platelet-derived growth factor (PDGF) signaling recruits the p85 subunit of Phosphoinositide 3-kinase (PI3K) to regulate mammalian lens development. Activation of PI3K signaling not only prevents B-cell lymphoma 2 (BCL2)-Associated X (Bax)- and BCL2 Antagonist/Killer (Bak)-mediated apoptosis but also promotes Notch signaling to prevent premature cell differentiation. Reducing PI3K activity destabilizes the Notch intracellular domain, while the constitutive activation of Notch reverses the PI3K deficiency phenotype. In contrast, fibroblast growth factor receptors (FGFRs) recruit Fibroblast Growth Factor Receptor Substrate 2 (Frs2) and Rous sarcoma oncogene (Src) Homology Phosphatase 2 (Shp2) to activate Mitogen-Activated Protein Kinase (MAPK) signaling, which induces the Notch ligand Jagged 1 (Jag1) and promotes cell differentiation. Inactivation of Shp2 restored the proper timing of differentiation in the p85 mutant lens, demonstrating the antagonistic interaction between FGF-induced MAPK and PDGF-induced PI3K signaling. By selective activation of PI3K and MAPK, PDGF and FGF cooperate with and oppose each other to balance progenitor cell maintenance and differentiation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30716082</pmid><doi>10.1371/journal.pbio.3000133</doi><orcidid>https://orcid.org/0000-0001-5555-0825</orcidid><orcidid>https://orcid.org/0000-0001-5182-7401</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1545-7885 |
| ispartof | PLoS biology, 2019-02, Vol.17 (2), p.e3000133-e3000133 |
| issn | 1545-7885 1544-9173 1545-7885 |
| language | eng |
| recordid | cdi_plos_journals_2249959910 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 1-Phosphatidylinositol 3-kinase Activation Animals Apoptosis B-cell lymphoma Bax protein bcl-2 Homologous Antagonist-Killer Protein - genetics bcl-2-Associated X Protein - genetics Biology Biology and Life Sciences Cell cycle Cell Differentiation Cell fate Cell growth Cell Survival Cells (biology) Deactivation Departments Differentiation (biology) Epithelial Cells - cytology Epithelial Cells - metabolism Fibroblast growth factor receptors Fibroblast growth factors Fibroblast Growth Factors - metabolism Fibroblasts Genes Growth factor receptors Growth factors Homology Inactivation Kinases Lens, Crystalline - cytology Lens, Crystalline - embryology Lens, Crystalline - metabolism Lenses Ligands Lymphocytes B Lymphoma Mammals MAP kinase MAP Kinase Signaling System Medicine and Health Sciences Mice Mutation - genetics Observations Pathology Phenotypes Phosphatidylinositol 3-Kinases - metabolism Physiological aspects Platelet-derived growth factor Platelet-Derived Growth Factor - metabolism Progenitor cells Protein Domains Protein kinase Protein Stability Proteins Proto-Oncogene Proteins c-akt - metabolism Receptor, Platelet-Derived Growth Factor alpha - metabolism Receptors Receptors, Notch - chemistry Receptors, Notch - metabolism Rous sarcoma Sarcoma Signal Transduction Signaling Substrates Tyrosine |
| title | Lens differentiation is controlled by the balance between PDGF and FGF signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T21%3A50%3A14IST&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=Lens%20differentiation%20is%20controlled%20by%20the%20balance%20between%20PDGF%20and%20FGF%20signaling&rft.jtitle=PLoS%20biology&rft.au=Li,%20Hongge&rft.date=2019-02-04&rft.volume=17&rft.issue=2&rft.spage=e3000133&rft.epage=e3000133&rft.pages=e3000133-e3000133&rft.issn=1545-7885&rft.eissn=1545-7885&rft_id=info:doi/10.1371/journal.pbio.3000133&rft_dat=%3Cgale_plos_%3EA577280354%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=2249959910&rft_id=info:pmid/30716082&rft_galeid=A577280354&rft_doaj_id=oai_doaj_org_article_e53aadeef79f4fda8bd5a2c6a6c8616e&rfr_iscdi=true |