Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain
- Autores
- Bauer, Angelika F.; Sonzogni, Silvina Veronica; Meyer, Lucas; Zeuzem, Stefan; Piiper, Albrecht; Biondi, Ricardo Miguel; Neimanis, Sonja
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Protein kinase C-related protein kinases (PRKs) are effectors of the Rho family of small GTPases and play a role in the development of diseases such as prostate cancer and hepatitis C. Here we examined the mechanism underlying the regulation of PRK2 by its N-terminal region. We show that the N-terminal region of PRK2 prevents the interaction with its upstream kinase, the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2. We confirm that the N-terminal region directly inhibits the kinase activity of PRK2. However, in contrast to previous models, our data indicate that this inhibition is mediated in trans through an intermolecular PRK2-PRK2 interaction. Our results also suggest that amino acids 487-501, located in the linker region between the N-terminal domains and the catalytic domain, contribute to the PRK2-PRK2 dimer formation. This dimerization is further supported by other N-terminal domains. Additionally, we provide evidence that the region C-terminal to the catalytic domain intramolecularly activates PRK2. Finally, we discovered that the catalytic domain mediates a cross-talk between the inhibitory N-terminal region and the activating C-terminal region. The results presented here describe a novel mechanism of regulation among AGC kinases and offer new insights into potential approaches to pharmacologically regulate PRK2.
Fil: Bauer, Angelika F.. Goethe Universitat Frankfurt; Alemania
Fil: Sonzogni, Silvina Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; Alemania
Fil: Meyer, Lucas. Goethe Universitat Frankfurt; Alemania
Fil: Zeuzem, Stefan. Goethe Universitat Frankfurt; Alemania
Fil: Piiper, Albrecht. Goethe Universitat Frankfurt; Alemania
Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; Alemania
Fil: Neimanis, Sonja. Goethe Universitat Frankfurt; Alemania - Materia
-
PRK2
REGULATION
DIMER
PDK1 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/216618
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
spelling |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domainBauer, Angelika F.Sonzogni, Silvina VeronicaMeyer, LucasZeuzem, StefanPiiper, AlbrechtBiondi, Ricardo MiguelNeimanis, SonjaPRK2REGULATIONDIMERPDK1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Protein kinase C-related protein kinases (PRKs) are effectors of the Rho family of small GTPases and play a role in the development of diseases such as prostate cancer and hepatitis C. Here we examined the mechanism underlying the regulation of PRK2 by its N-terminal region. We show that the N-terminal region of PRK2 prevents the interaction with its upstream kinase, the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2. We confirm that the N-terminal region directly inhibits the kinase activity of PRK2. However, in contrast to previous models, our data indicate that this inhibition is mediated in trans through an intermolecular PRK2-PRK2 interaction. Our results also suggest that amino acids 487-501, located in the linker region between the N-terminal domains and the catalytic domain, contribute to the PRK2-PRK2 dimer formation. This dimerization is further supported by other N-terminal domains. Additionally, we provide evidence that the region C-terminal to the catalytic domain intramolecularly activates PRK2. Finally, we discovered that the catalytic domain mediates a cross-talk between the inhibitory N-terminal region and the activating C-terminal region. The results presented here describe a novel mechanism of regulation among AGC kinases and offer new insights into potential approaches to pharmacologically regulate PRK2.Fil: Bauer, Angelika F.. Goethe Universitat Frankfurt; AlemaniaFil: Sonzogni, Silvina Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; AlemaniaFil: Meyer, Lucas. Goethe Universitat Frankfurt; AlemaniaFil: Zeuzem, Stefan. Goethe Universitat Frankfurt; AlemaniaFil: Piiper, Albrecht. Goethe Universitat Frankfurt; AlemaniaFil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; AlemaniaFil: Neimanis, Sonja. Goethe Universitat Frankfurt; AlemaniaAmerican Society for Biochemistry and Molecular Biology2012-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/216618Bauer, Angelika F.; Sonzogni, Silvina Veronica; Meyer, Lucas; Zeuzem, Stefan; Piiper, Albrecht; et al.; Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 287; 24; 6-2012; 20590-206020021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/287/24/20590.longinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M111.327437info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:00:04Zoai:ri.conicet.gov.ar:11336/216618instacron: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:34982025-10-22 12:00:05.019CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain |
title |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain |
spellingShingle |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain Bauer, Angelika F. PRK2 REGULATION DIMER PDK1 |
title_short |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain |
title_full |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain |
title_fullStr |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain |
title_full_unstemmed |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain |
title_sort |
Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain |
dc.creator.none.fl_str_mv |
Bauer, Angelika F. Sonzogni, Silvina Veronica Meyer, Lucas Zeuzem, Stefan Piiper, Albrecht Biondi, Ricardo Miguel Neimanis, Sonja |
author |
Bauer, Angelika F. |
author_facet |
Bauer, Angelika F. Sonzogni, Silvina Veronica Meyer, Lucas Zeuzem, Stefan Piiper, Albrecht Biondi, Ricardo Miguel Neimanis, Sonja |
author_role |
author |
author2 |
Sonzogni, Silvina Veronica Meyer, Lucas Zeuzem, Stefan Piiper, Albrecht Biondi, Ricardo Miguel Neimanis, Sonja |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
PRK2 REGULATION DIMER PDK1 |
topic |
PRK2 REGULATION DIMER PDK1 |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Protein kinase C-related protein kinases (PRKs) are effectors of the Rho family of small GTPases and play a role in the development of diseases such as prostate cancer and hepatitis C. Here we examined the mechanism underlying the regulation of PRK2 by its N-terminal region. We show that the N-terminal region of PRK2 prevents the interaction with its upstream kinase, the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2. We confirm that the N-terminal region directly inhibits the kinase activity of PRK2. However, in contrast to previous models, our data indicate that this inhibition is mediated in trans through an intermolecular PRK2-PRK2 interaction. Our results also suggest that amino acids 487-501, located in the linker region between the N-terminal domains and the catalytic domain, contribute to the PRK2-PRK2 dimer formation. This dimerization is further supported by other N-terminal domains. Additionally, we provide evidence that the region C-terminal to the catalytic domain intramolecularly activates PRK2. Finally, we discovered that the catalytic domain mediates a cross-talk between the inhibitory N-terminal region and the activating C-terminal region. The results presented here describe a novel mechanism of regulation among AGC kinases and offer new insights into potential approaches to pharmacologically regulate PRK2. Fil: Bauer, Angelika F.. Goethe Universitat Frankfurt; Alemania Fil: Sonzogni, Silvina Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; Alemania Fil: Meyer, Lucas. Goethe Universitat Frankfurt; Alemania Fil: Zeuzem, Stefan. Goethe Universitat Frankfurt; Alemania Fil: Piiper, Albrecht. Goethe Universitat Frankfurt; Alemania Fil: Biondi, Ricardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Goethe Universitat Frankfurt; Alemania Fil: Neimanis, Sonja. Goethe Universitat Frankfurt; Alemania |
description |
Protein kinase C-related protein kinases (PRKs) are effectors of the Rho family of small GTPases and play a role in the development of diseases such as prostate cancer and hepatitis C. Here we examined the mechanism underlying the regulation of PRK2 by its N-terminal region. We show that the N-terminal region of PRK2 prevents the interaction with its upstream kinase, the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2. We confirm that the N-terminal region directly inhibits the kinase activity of PRK2. However, in contrast to previous models, our data indicate that this inhibition is mediated in trans through an intermolecular PRK2-PRK2 interaction. Our results also suggest that amino acids 487-501, located in the linker region between the N-terminal domains and the catalytic domain, contribute to the PRK2-PRK2 dimer formation. This dimerization is further supported by other N-terminal domains. Additionally, we provide evidence that the region C-terminal to the catalytic domain intramolecularly activates PRK2. Finally, we discovered that the catalytic domain mediates a cross-talk between the inhibitory N-terminal region and the activating C-terminal region. The results presented here describe a novel mechanism of regulation among AGC kinases and offer new insights into potential approaches to pharmacologically regulate PRK2. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-06 |
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/11336/216618 Bauer, Angelika F.; Sonzogni, Silvina Veronica; Meyer, Lucas; Zeuzem, Stefan; Piiper, Albrecht; et al.; Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 287; 24; 6-2012; 20590-20602 0021-9258 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/216618 |
identifier_str_mv |
Bauer, Angelika F.; Sonzogni, Silvina Veronica; Meyer, Lucas; Zeuzem, Stefan; Piiper, Albrecht; et al.; Regulation of protein kinase C-related Protein Kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by its N-terminal domain; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 287; 24; 6-2012; 20590-20602 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/287/24/20590.long info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M111.327437 |
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 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 |
12.982451 |