Bone Morphogenetic Protein 2 Stimulates Noncanonical SMAD2/3 Signaling via the BMP Type 1A Receptor in Gonadotrope-Like Cells: Implications for FSH Synthesis
FSH is an essential regulator of mammalian reproduction. Its synthesis by pituitary gonadotrope cells is regulated by multiple endocrine and paracrine factors, including TGFβ superfamily ligands, such as the activins and inhibins. Activins stimulate FSH synthesis via transcriptional regulation of it...
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creator | Wang, Ying Ho, Catherine C Bang, EunJin Rejon, Carlis A Libasci, Vanessa Pertchenko, Pavel Hébert, Terence E Bernard, Daniel J |
description | FSH is an essential regulator of mammalian reproduction. Its synthesis by pituitary gonadotrope cells is regulated by multiple endocrine and paracrine factors, including TGFβ superfamily ligands, such as the activins and inhibins. Activins stimulate FSH synthesis via transcriptional regulation of its β-subunit gene (Fshb). More recently, bone morphogenetic proteins (BMPs) were shown to stimulate murine Fshb transcription alone and in synergy with activins. BMP2 signals via its canonical type I receptor, BMPR1A (or activin receptor-like kinase 3 [ALK3]), and SMAD1 and SMAD5 to stimulate transcription of inhibitor of DNA binding proteins. Inhibitor of DNA binding proteins then potentiate the actions of activin-stimulated SMAD3 to regulate the Fshb gene in the gonadotrope-like LβT2 cell line. Here, we report the unexpected observation that BMP2 also stimulates the SMAD2/3 pathway in these cells and that it does so directly via ALK3. Indeed, this novel, noncanonical ALK3 activity is completely independent of ALK4, ALK5, and ALK7, the type I receptors most often associated with SMAD2/3 pathway activation. Induction of the SMAD2/3 pathway by ALK3 is dependent upon its own previous activation by associated type II receptors, which phosphorylate conserved serine and threonine residues in the ALK3 juxtamembrane glycine-serine-rich domain. ALK3 signaling via SMAD3 is necessary for the receptor to stimulate Fshb transcription, whereas its activation of the SMAD1/5/8 pathway alone is insufficient. These data challenge current dogma that ALK3 and other BMP type I receptors signal via SMAD1, SMAD5, and SMAD8 and not SMAD2 or SMAD3. Moreover, they suggest that BMPs and activins may use similar intracellular signaling mechanisms to activate the murine Fshb promoter in immortalized gonadotrope-like cells. |
doi_str_mv | 10.1210/en.2013-1741 |
format | Article |
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Its synthesis by pituitary gonadotrope cells is regulated by multiple endocrine and paracrine factors, including TGFβ superfamily ligands, such as the activins and inhibins. Activins stimulate FSH synthesis via transcriptional regulation of its β-subunit gene (Fshb). More recently, bone morphogenetic proteins (BMPs) were shown to stimulate murine Fshb transcription alone and in synergy with activins. BMP2 signals via its canonical type I receptor, BMPR1A (or activin receptor-like kinase 3 [ALK3]), and SMAD1 and SMAD5 to stimulate transcription of inhibitor of DNA binding proteins. Inhibitor of DNA binding proteins then potentiate the actions of activin-stimulated SMAD3 to regulate the Fshb gene in the gonadotrope-like LβT2 cell line. Here, we report the unexpected observation that BMP2 also stimulates the SMAD2/3 pathway in these cells and that it does so directly via ALK3. Indeed, this novel, noncanonical ALK3 activity is completely independent of ALK4, ALK5, and ALK7, the type I receptors most often associated with SMAD2/3 pathway activation. Induction of the SMAD2/3 pathway by ALK3 is dependent upon its own previous activation by associated type II receptors, which phosphorylate conserved serine and threonine residues in the ALK3 juxtamembrane glycine-serine-rich domain. ALK3 signaling via SMAD3 is necessary for the receptor to stimulate Fshb transcription, whereas its activation of the SMAD1/5/8 pathway alone is insufficient. These data challenge current dogma that ALK3 and other BMP type I receptors signal via SMAD1, SMAD5, and SMAD8 and not SMAD2 or SMAD3. Moreover, they suggest that BMPs and activins may use similar intracellular signaling mechanisms to activate the murine Fshb promoter in immortalized gonadotrope-like cells.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2013-1741</identifier><identifier>PMID: 24601881</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Activin ; Activins - antagonists & inhibitors ; Activins - metabolism ; Animals ; Binding ; Bone morphogenetic protein 2 ; Bone Morphogenetic Protein 2 - agonists ; Bone Morphogenetic Protein 2 - antagonists & inhibitors ; Bone Morphogenetic Protein 2 - genetics ; Bone Morphogenetic Protein 2 - metabolism ; Bone morphogenetic protein receptor type I ; Bone Morphogenetic Protein Receptors, Type I - agonists ; Bone Morphogenetic Protein Receptors, Type I - antagonists & inhibitors ; Bone Morphogenetic Protein Receptors, Type I - genetics ; Bone Morphogenetic Protein Receptors, Type I - metabolism ; Bone morphogenetic proteins ; Cell Line ; Deoxyribonucleic acid ; DNA ; Follicle Stimulating Hormone, beta Subunit - biosynthesis ; Follicle Stimulating Hormone, beta Subunit - genetics ; Follicle Stimulating Hormone, beta Subunit - metabolism ; Follicle-stimulating hormone ; Gene regulation ; Gene Silencing ; Genes, Reporter ; Glycine ; Gonadotrophs - metabolism ; Humans ; Intracellular signalling ; Kinases ; Mice ; Paracrine signalling ; Phosphorylation ; Pituitary ; Pituitary (anterior) ; Protein Processing, Post-Translational ; Proteins ; Receptors ; Recombinant Proteins - chemistry ; Recombinant Proteins - metabolism ; RNA, Small Interfering ; Serine ; Signal Transduction ; Smad2 protein ; Smad2 Protein - antagonists & inhibitors ; Smad2 Protein - genetics ; Smad2 Protein - metabolism ; Smad3 protein ; Smad3 Protein - antagonists & inhibitors ; Smad3 Protein - genetics ; Smad3 Protein - metabolism ; Smad5 protein ; Synthesis ; Transcription activation ; Transcription factors ; Transcription, Genetic</subject><ispartof>Endocrinology (Philadelphia), 2014-05, Vol.155 (5), p.1970-1981</ispartof><rights>Copyright © 2014 by the Endocrine Society</rights><rights>Copyright © 2014 by the Endocrine Society 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-ffb4d136ef487ecfbc3316f462379bbb5c8eb27037b4c3f408820bf3651662533</citedby><cites>FETCH-LOGICAL-c499t-ffb4d136ef487ecfbc3316f462379bbb5c8eb27037b4c3f408820bf3651662533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24601881$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Ho, Catherine C</creatorcontrib><creatorcontrib>Bang, EunJin</creatorcontrib><creatorcontrib>Rejon, Carlis A</creatorcontrib><creatorcontrib>Libasci, Vanessa</creatorcontrib><creatorcontrib>Pertchenko, Pavel</creatorcontrib><creatorcontrib>Hébert, Terence E</creatorcontrib><creatorcontrib>Bernard, Daniel J</creatorcontrib><title>Bone Morphogenetic Protein 2 Stimulates Noncanonical SMAD2/3 Signaling via the BMP Type 1A Receptor in Gonadotrope-Like Cells: Implications for FSH Synthesis</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>FSH is an essential regulator of mammalian reproduction. Its synthesis by pituitary gonadotrope cells is regulated by multiple endocrine and paracrine factors, including TGFβ superfamily ligands, such as the activins and inhibins. Activins stimulate FSH synthesis via transcriptional regulation of its β-subunit gene (Fshb). More recently, bone morphogenetic proteins (BMPs) were shown to stimulate murine Fshb transcription alone and in synergy with activins. BMP2 signals via its canonical type I receptor, BMPR1A (or activin receptor-like kinase 3 [ALK3]), and SMAD1 and SMAD5 to stimulate transcription of inhibitor of DNA binding proteins. Inhibitor of DNA binding proteins then potentiate the actions of activin-stimulated SMAD3 to regulate the Fshb gene in the gonadotrope-like LβT2 cell line. Here, we report the unexpected observation that BMP2 also stimulates the SMAD2/3 pathway in these cells and that it does so directly via ALK3. Indeed, this novel, noncanonical ALK3 activity is completely independent of ALK4, ALK5, and ALK7, the type I receptors most often associated with SMAD2/3 pathway activation. Induction of the SMAD2/3 pathway by ALK3 is dependent upon its own previous activation by associated type II receptors, which phosphorylate conserved serine and threonine residues in the ALK3 juxtamembrane glycine-serine-rich domain. ALK3 signaling via SMAD3 is necessary for the receptor to stimulate Fshb transcription, whereas its activation of the SMAD1/5/8 pathway alone is insufficient. These data challenge current dogma that ALK3 and other BMP type I receptors signal via SMAD1, SMAD5, and SMAD8 and not SMAD2 or SMAD3. Moreover, they suggest that BMPs and activins may use similar intracellular signaling mechanisms to activate the murine Fshb promoter in immortalized gonadotrope-like cells.</description><subject>Activin</subject><subject>Activins - antagonists & inhibitors</subject><subject>Activins - metabolism</subject><subject>Animals</subject><subject>Binding</subject><subject>Bone morphogenetic protein 2</subject><subject>Bone Morphogenetic Protein 2 - agonists</subject><subject>Bone Morphogenetic Protein 2 - antagonists & inhibitors</subject><subject>Bone Morphogenetic Protein 2 - genetics</subject><subject>Bone Morphogenetic Protein 2 - metabolism</subject><subject>Bone morphogenetic protein receptor type I</subject><subject>Bone Morphogenetic Protein Receptors, Type I - agonists</subject><subject>Bone Morphogenetic Protein Receptors, Type I - antagonists & inhibitors</subject><subject>Bone Morphogenetic Protein Receptors, Type I - genetics</subject><subject>Bone Morphogenetic Protein Receptors, Type I - metabolism</subject><subject>Bone morphogenetic proteins</subject><subject>Cell Line</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Follicle Stimulating Hormone, beta Subunit - biosynthesis</subject><subject>Follicle Stimulating Hormone, beta Subunit - genetics</subject><subject>Follicle Stimulating Hormone, beta Subunit - metabolism</subject><subject>Follicle-stimulating hormone</subject><subject>Gene regulation</subject><subject>Gene Silencing</subject><subject>Genes, Reporter</subject><subject>Glycine</subject><subject>Gonadotrophs - metabolism</subject><subject>Humans</subject><subject>Intracellular signalling</subject><subject>Kinases</subject><subject>Mice</subject><subject>Paracrine signalling</subject><subject>Phosphorylation</subject><subject>Pituitary</subject><subject>Pituitary (anterior)</subject><subject>Protein Processing, Post-Translational</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - metabolism</subject><subject>RNA, Small Interfering</subject><subject>Serine</subject><subject>Signal Transduction</subject><subject>Smad2 protein</subject><subject>Smad2 Protein - antagonists & inhibitors</subject><subject>Smad2 Protein - genetics</subject><subject>Smad2 Protein - metabolism</subject><subject>Smad3 protein</subject><subject>Smad3 Protein - antagonists & inhibitors</subject><subject>Smad3 Protein - genetics</subject><subject>Smad3 Protein - metabolism</subject><subject>Smad5 protein</subject><subject>Synthesis</subject><subject>Transcription activation</subject><subject>Transcription factors</subject><subject>Transcription, Genetic</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1v1DAQhi0EokvhxhlZ4gAH0vorcdLbdks_pF2oSDlHiXe8dUnsYDuV9sfwX_FqF5AQnEYzevTo1bwIvabkhDJKTsGeMEJ5RqWgT9CMViLPJJXkKZqR3V0yJo_QixAe0iqE4M_RERMFoWVJZ-jHubOAV86P924DFqJR-Na7CMZihutohqlvIwT8yVnVWmeNantcr-YX7JTj2mxs2xu7wY-mxfEe8PnqFt9tR8B0jr-AgjE6j5Prytl27aJ3I2RL8w3wAvo-nOGbYeyTMhpnA9aJvayvcb21yRVMeIme6bYP8Oowj9HXy493i-ts-fnqZjFfZkpUVcy07sSa8gK0KCUo3SnOaaFFwbisuq7LVQkdk4TLTiiuBSlLRjrNi5wWBcs5P0bv997Ru-8ThNgMJqiUsLXgptDQnJZMCCaqhL79C31wk09fCA2nnEiSEuWJ-rCnlHcheNDN6M3Q-m1DSbOrrQHb7GprdrUl_M1BOnUDrH_Dv3pKwLs94Kbxf6rsoOJ7EuzaKW8sjB5C-JPynwF-AhmbrqE</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Wang, Ying</creator><creator>Ho, Catherine C</creator><creator>Bang, EunJin</creator><creator>Rejon, Carlis A</creator><creator>Libasci, Vanessa</creator><creator>Pertchenko, Pavel</creator><creator>Hébert, Terence E</creator><creator>Bernard, Daniel J</creator><general>Endocrine Society</general><general>Oxford University Press</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20140501</creationdate><title>Bone Morphogenetic Protein 2 Stimulates Noncanonical SMAD2/3 Signaling via the BMP Type 1A Receptor in Gonadotrope-Like Cells: Implications for FSH Synthesis</title><author>Wang, Ying ; Ho, Catherine C ; Bang, EunJin ; Rejon, Carlis A ; Libasci, Vanessa ; Pertchenko, Pavel ; Hébert, Terence E ; Bernard, Daniel J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-ffb4d136ef487ecfbc3316f462379bbb5c8eb27037b4c3f408820bf3651662533</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Activin</topic><topic>Activins - antagonists & inhibitors</topic><topic>Activins - metabolism</topic><topic>Animals</topic><topic>Binding</topic><topic>Bone morphogenetic protein 2</topic><topic>Bone Morphogenetic Protein 2 - agonists</topic><topic>Bone Morphogenetic Protein 2 - antagonists & inhibitors</topic><topic>Bone Morphogenetic Protein 2 - genetics</topic><topic>Bone Morphogenetic Protein 2 - metabolism</topic><topic>Bone morphogenetic protein receptor type I</topic><topic>Bone Morphogenetic Protein Receptors, Type I - agonists</topic><topic>Bone Morphogenetic Protein Receptors, Type I - antagonists & inhibitors</topic><topic>Bone Morphogenetic Protein Receptors, Type I - genetics</topic><topic>Bone Morphogenetic Protein Receptors, Type I - metabolism</topic><topic>Bone morphogenetic proteins</topic><topic>Cell Line</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Follicle Stimulating Hormone, beta Subunit - biosynthesis</topic><topic>Follicle Stimulating Hormone, beta Subunit - genetics</topic><topic>Follicle Stimulating Hormone, beta Subunit - metabolism</topic><topic>Follicle-stimulating hormone</topic><topic>Gene regulation</topic><topic>Gene Silencing</topic><topic>Genes, Reporter</topic><topic>Glycine</topic><topic>Gonadotrophs - metabolism</topic><topic>Humans</topic><topic>Intracellular signalling</topic><topic>Kinases</topic><topic>Mice</topic><topic>Paracrine signalling</topic><topic>Phosphorylation</topic><topic>Pituitary</topic><topic>Pituitary (anterior)</topic><topic>Protein Processing, Post-Translational</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Recombinant Proteins - chemistry</topic><topic>Recombinant Proteins - metabolism</topic><topic>RNA, Small Interfering</topic><topic>Serine</topic><topic>Signal Transduction</topic><topic>Smad2 protein</topic><topic>Smad2 Protein - antagonists & inhibitors</topic><topic>Smad2 Protein - genetics</topic><topic>Smad2 Protein - metabolism</topic><topic>Smad3 protein</topic><topic>Smad3 Protein - antagonists & inhibitors</topic><topic>Smad3 Protein - genetics</topic><topic>Smad3 Protein - metabolism</topic><topic>Smad5 protein</topic><topic>Synthesis</topic><topic>Transcription activation</topic><topic>Transcription factors</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Ho, Catherine C</creatorcontrib><creatorcontrib>Bang, EunJin</creatorcontrib><creatorcontrib>Rejon, Carlis A</creatorcontrib><creatorcontrib>Libasci, Vanessa</creatorcontrib><creatorcontrib>Pertchenko, Pavel</creatorcontrib><creatorcontrib>Hébert, Terence E</creatorcontrib><creatorcontrib>Bernard, Daniel J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Ying</au><au>Ho, Catherine C</au><au>Bang, EunJin</au><au>Rejon, Carlis A</au><au>Libasci, Vanessa</au><au>Pertchenko, Pavel</au><au>Hébert, Terence E</au><au>Bernard, Daniel J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone Morphogenetic Protein 2 Stimulates Noncanonical SMAD2/3 Signaling via the BMP Type 1A Receptor in Gonadotrope-Like Cells: Implications for FSH Synthesis</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>155</volume><issue>5</issue><spage>1970</spage><epage>1981</epage><pages>1970-1981</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><abstract>FSH is an essential regulator of mammalian reproduction. Its synthesis by pituitary gonadotrope cells is regulated by multiple endocrine and paracrine factors, including TGFβ superfamily ligands, such as the activins and inhibins. Activins stimulate FSH synthesis via transcriptional regulation of its β-subunit gene (Fshb). More recently, bone morphogenetic proteins (BMPs) were shown to stimulate murine Fshb transcription alone and in synergy with activins. BMP2 signals via its canonical type I receptor, BMPR1A (or activin receptor-like kinase 3 [ALK3]), and SMAD1 and SMAD5 to stimulate transcription of inhibitor of DNA binding proteins. Inhibitor of DNA binding proteins then potentiate the actions of activin-stimulated SMAD3 to regulate the Fshb gene in the gonadotrope-like LβT2 cell line. Here, we report the unexpected observation that BMP2 also stimulates the SMAD2/3 pathway in these cells and that it does so directly via ALK3. Indeed, this novel, noncanonical ALK3 activity is completely independent of ALK4, ALK5, and ALK7, the type I receptors most often associated with SMAD2/3 pathway activation. Induction of the SMAD2/3 pathway by ALK3 is dependent upon its own previous activation by associated type II receptors, which phosphorylate conserved serine and threonine residues in the ALK3 juxtamembrane glycine-serine-rich domain. ALK3 signaling via SMAD3 is necessary for the receptor to stimulate Fshb transcription, whereas its activation of the SMAD1/5/8 pathway alone is insufficient. These data challenge current dogma that ALK3 and other BMP type I receptors signal via SMAD1, SMAD5, and SMAD8 and not SMAD2 or SMAD3. Moreover, they suggest that BMPs and activins may use similar intracellular signaling mechanisms to activate the murine Fshb promoter in immortalized gonadotrope-like cells.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>24601881</pmid><doi>10.1210/en.2013-1741</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Journals@Ovid Complete; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Activin Activins - antagonists & inhibitors Activins - metabolism Animals Binding Bone morphogenetic protein 2 Bone Morphogenetic Protein 2 - agonists Bone Morphogenetic Protein 2 - antagonists & inhibitors Bone Morphogenetic Protein 2 - genetics Bone Morphogenetic Protein 2 - metabolism Bone morphogenetic protein receptor type I Bone Morphogenetic Protein Receptors, Type I - agonists Bone Morphogenetic Protein Receptors, Type I - antagonists & inhibitors Bone Morphogenetic Protein Receptors, Type I - genetics Bone Morphogenetic Protein Receptors, Type I - metabolism Bone morphogenetic proteins Cell Line Deoxyribonucleic acid DNA Follicle Stimulating Hormone, beta Subunit - biosynthesis Follicle Stimulating Hormone, beta Subunit - genetics Follicle Stimulating Hormone, beta Subunit - metabolism Follicle-stimulating hormone Gene regulation Gene Silencing Genes, Reporter Glycine Gonadotrophs - metabolism Humans Intracellular signalling Kinases Mice Paracrine signalling Phosphorylation Pituitary Pituitary (anterior) Protein Processing, Post-Translational Proteins Receptors Recombinant Proteins - chemistry Recombinant Proteins - metabolism RNA, Small Interfering Serine Signal Transduction Smad2 protein Smad2 Protein - antagonists & inhibitors Smad2 Protein - genetics Smad2 Protein - metabolism Smad3 protein Smad3 Protein - antagonists & inhibitors Smad3 Protein - genetics Smad3 Protein - metabolism Smad5 protein Synthesis Transcription activation Transcription factors Transcription, Genetic |
title | Bone Morphogenetic Protein 2 Stimulates Noncanonical SMAD2/3 Signaling via the BMP Type 1A Receptor in Gonadotrope-Like Cells: Implications for FSH Synthesis |
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