Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase

Autores
Sangeeta Devi, Y.; Seibold, Anita M.; Shehu, Aurora; Maizels, Evelyn; Halperin, Julia; Le, Jamie; Binart, Nadine; Bao, Lei; Gibori, Geula
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Prolactin (PRL) is essential for normal reproduction and signals through two types of receptors, the short (PRL-RS) and long (PRL-RL) form. We have previously shown that transgenic mice expressing only PRL-RS (PRLR-/-RS) display abnormal follicular development and premature ovarian failure. Here, we report that MAPK, essential for normal follicular development, is critically inhibited by PRL in reproductive tissues of PRLR-/-RS mice. Consequently, the phosphorylation of MAPK downstream targets are also markedly inhibited by PRL without affecting immediate upstream kinases, suggesting involvement of MAPK specific phosphatase(s) in this inhibition. Similar results are obtained in a PRL responsive ovarian derived cell line (GG-CL) that expresses only PRL-RS. However, we found the expression/activation of several known MAPK phosphatases not to be affected by PRL, suggesting a role of unidentified phosphatas(s). We detected a 27KDa protein that binds to the intracellular domain of PRL-RS and identified it as dual specific phosphatase DUPD1. PRL does not induce expression of DUDP1 but represses its phosphorylation on T155. We also show a physical association of this phosphatase with ERK1/2 and p38 MAPK. Using an in vitro phosphatase assay and overexpression studies, we established that DUPD1 is a MAPK phosphatase. Dual specific phosphatase inhibitors as well as siRNA to DUPD1, completely prevent PRL mediated MAPK inhibition in ovarian cells. Our results strongly suggest that deactivation of MAPK by PRL/PRL-RS contributes to the severe ovarian defect in PRLR-/-RS mice and demonstrate the novel association of PRL-RS with DUPD1 and a role for this phosphatase in MAPK deactivation.
Fil: Sangeeta Devi, Y.. University of Illinois at Urbana; Estados Unidos
Fil: Seibold, Anita M.. University of Illinois at Urbana; Estados Unidos
Fil: Shehu, Aurora. University of Illinois at Urbana; Estados Unidos
Fil: Maizels, Evelyn. University of Illinois at Urbana; Estados Unidos
Fil: Halperin, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Le, Jamie. University of Illinois at Urbana; Estados Unidos
Fil: Binart, Nadine. University of Illinois at Urbana; Estados Unidos
Fil: Bao, Lei. University of Illinois at Urbana; Estados Unidos
Fil: Gibori, Geula. University of Illinois at Urbana; Estados Unidos
Materia
Prolactin
prolactin receptor
MAPK
ovary
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/192406
Acceder
id CONICETDig_a403016bb14cd2b7e8e78a7138793838
oai_identifier_str oai:ri.conicet.gov.ar:11336/192406
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphataseSangeeta Devi, Y.Seibold, Anita M.Shehu, AuroraMaizels, EvelynHalperin, JuliaLe, JamieBinart, NadineBao, LeiGibori, GeulaProlactinprolactin receptorMAPKovaryhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Prolactin (PRL) is essential for normal reproduction and signals through two types of receptors, the short (PRL-RS) and long (PRL-RL) form. We have previously shown that transgenic mice expressing only PRL-RS (PRLR-/-RS) display abnormal follicular development and premature ovarian failure. Here, we report that MAPK, essential for normal follicular development, is critically inhibited by PRL in reproductive tissues of PRLR-/-RS mice. Consequently, the phosphorylation of MAPK downstream targets are also markedly inhibited by PRL without affecting immediate upstream kinases, suggesting involvement of MAPK specific phosphatase(s) in this inhibition. Similar results are obtained in a PRL responsive ovarian derived cell line (GG-CL) that expresses only PRL-RS. However, we found the expression/activation of several known MAPK phosphatases not to be affected by PRL, suggesting a role of unidentified phosphatas(s). We detected a 27KDa protein that binds to the intracellular domain of PRL-RS and identified it as dual specific phosphatase DUPD1. PRL does not induce expression of DUDP1 but represses its phosphorylation on T155. We also show a physical association of this phosphatase with ERK1/2 and p38 MAPK. Using an in vitro phosphatase assay and overexpression studies, we established that DUPD1 is a MAPK phosphatase. Dual specific phosphatase inhibitors as well as siRNA to DUPD1, completely prevent PRL mediated MAPK inhibition in ovarian cells. Our results strongly suggest that deactivation of MAPK by PRL/PRL-RS contributes to the severe ovarian defect in PRLR-/-RS mice and demonstrate the novel association of PRL-RS with DUPD1 and a role for this phosphatase in MAPK deactivation.Fil: Sangeeta Devi, Y.. University of Illinois at Urbana; Estados UnidosFil: Seibold, Anita M.. University of Illinois at Urbana; Estados UnidosFil: Shehu, Aurora. University of Illinois at Urbana; Estados UnidosFil: Maizels, Evelyn. University of Illinois at Urbana; Estados UnidosFil: Halperin, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Le, Jamie. University of Illinois at Urbana; Estados UnidosFil: Binart, Nadine. University of Illinois at Urbana; Estados UnidosFil: Bao, Lei. University of Illinois at Urbana; Estados UnidosFil: Gibori, Geula. University of Illinois at Urbana; Estados UnidosAmerican Society for Biochemistry and Molecular Biology2011-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/192406Sangeeta Devi, Y. ; Seibold, Anita M.; Shehu, Aurora; Maizels, Evelyn; Halperin, Julia; et al.; Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 286; 9; 4-2011; 7609-76180021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/286/9/7609.longinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M110.166603info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:27:34Zoai:ri.conicet.gov.ar:11336/192406instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:27:34.395CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
title Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
spellingShingle Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
Sangeeta Devi, Y.
Prolactin
prolactin receptor
MAPK
ovary
title_short Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
title_full Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
title_fullStr Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
title_full_unstemmed Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
title_sort Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase
dc.creator.none.fl_str_mv Sangeeta Devi, Y.
Seibold, Anita M.
Shehu, Aurora
Maizels, Evelyn
Halperin, Julia
Le, Jamie
Binart, Nadine
Bao, Lei
Gibori, Geula
author Sangeeta Devi, Y.
author_facet Sangeeta Devi, Y.
Seibold, Anita M.
Shehu, Aurora
Maizels, Evelyn
Halperin, Julia
Le, Jamie
Binart, Nadine
Bao, Lei
Gibori, Geula
author_role author
author2 Seibold, Anita M.
Shehu, Aurora
Maizels, Evelyn
Halperin, Julia
Le, Jamie
Binart, Nadine
Bao, Lei
Gibori, Geula
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Prolactin
prolactin receptor
MAPK
ovary
topic Prolactin
prolactin receptor
MAPK
ovary
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Prolactin (PRL) is essential for normal reproduction and signals through two types of receptors, the short (PRL-RS) and long (PRL-RL) form. We have previously shown that transgenic mice expressing only PRL-RS (PRLR-/-RS) display abnormal follicular development and premature ovarian failure. Here, we report that MAPK, essential for normal follicular development, is critically inhibited by PRL in reproductive tissues of PRLR-/-RS mice. Consequently, the phosphorylation of MAPK downstream targets are also markedly inhibited by PRL without affecting immediate upstream kinases, suggesting involvement of MAPK specific phosphatase(s) in this inhibition. Similar results are obtained in a PRL responsive ovarian derived cell line (GG-CL) that expresses only PRL-RS. However, we found the expression/activation of several known MAPK phosphatases not to be affected by PRL, suggesting a role of unidentified phosphatas(s). We detected a 27KDa protein that binds to the intracellular domain of PRL-RS and identified it as dual specific phosphatase DUPD1. PRL does not induce expression of DUDP1 but represses its phosphorylation on T155. We also show a physical association of this phosphatase with ERK1/2 and p38 MAPK. Using an in vitro phosphatase assay and overexpression studies, we established that DUPD1 is a MAPK phosphatase. Dual specific phosphatase inhibitors as well as siRNA to DUPD1, completely prevent PRL mediated MAPK inhibition in ovarian cells. Our results strongly suggest that deactivation of MAPK by PRL/PRL-RS contributes to the severe ovarian defect in PRLR-/-RS mice and demonstrate the novel association of PRL-RS with DUPD1 and a role for this phosphatase in MAPK deactivation.
Fil: Sangeeta Devi, Y.. University of Illinois at Urbana; Estados Unidos
Fil: Seibold, Anita M.. University of Illinois at Urbana; Estados Unidos
Fil: Shehu, Aurora. University of Illinois at Urbana; Estados Unidos
Fil: Maizels, Evelyn. University of Illinois at Urbana; Estados Unidos
Fil: Halperin, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Le, Jamie. University of Illinois at Urbana; Estados Unidos
Fil: Binart, Nadine. University of Illinois at Urbana; Estados Unidos
Fil: Bao, Lei. University of Illinois at Urbana; Estados Unidos
Fil: Gibori, Geula. University of Illinois at Urbana; Estados Unidos
description Prolactin (PRL) is essential for normal reproduction and signals through two types of receptors, the short (PRL-RS) and long (PRL-RL) form. We have previously shown that transgenic mice expressing only PRL-RS (PRLR-/-RS) display abnormal follicular development and premature ovarian failure. Here, we report that MAPK, essential for normal follicular development, is critically inhibited by PRL in reproductive tissues of PRLR-/-RS mice. Consequently, the phosphorylation of MAPK downstream targets are also markedly inhibited by PRL without affecting immediate upstream kinases, suggesting involvement of MAPK specific phosphatase(s) in this inhibition. Similar results are obtained in a PRL responsive ovarian derived cell line (GG-CL) that expresses only PRL-RS. However, we found the expression/activation of several known MAPK phosphatases not to be affected by PRL, suggesting a role of unidentified phosphatas(s). We detected a 27KDa protein that binds to the intracellular domain of PRL-RS and identified it as dual specific phosphatase DUPD1. PRL does not induce expression of DUDP1 but represses its phosphorylation on T155. We also show a physical association of this phosphatase with ERK1/2 and p38 MAPK. Using an in vitro phosphatase assay and overexpression studies, we established that DUPD1 is a MAPK phosphatase. Dual specific phosphatase inhibitors as well as siRNA to DUPD1, completely prevent PRL mediated MAPK inhibition in ovarian cells. Our results strongly suggest that deactivation of MAPK by PRL/PRL-RS contributes to the severe ovarian defect in PRLR-/-RS mice and demonstrate the novel association of PRL-RS with DUPD1 and a role for this phosphatase in MAPK deactivation.
publishDate 2011
dc.date.none.fl_str_mv 2011-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/192406
Sangeeta Devi, Y. ; Seibold, Anita M.; Shehu, Aurora; Maizels, Evelyn; Halperin, Julia; et al.; Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 286; 9; 4-2011; 7609-7618
0021-9258
CONICET Digital
CONICET
url http://hdl.handle.net/11336/192406
identifier_str_mv Sangeeta Devi, Y. ; Seibold, Anita M.; Shehu, Aurora; Maizels, Evelyn; Halperin, Julia; et al.; Inhibition of MAPK by prolactin signaling through the short form of its receptor in the ovary and decidua: Involvement of a novel phosphatase; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 286; 9; 4-2011; 7609-7618
0021-9258
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/286/9/7609.long
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M110.166603
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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