Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation

Autores
Battistone, Maria Agustina; Alvau, A.; Salicioni, A. M.; Visconti, P. E.; Da Ros, Vanina Gabriela; Cuasnicu, Patricia Sara
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sperm capacitation involves an increase in intracellular Ca(2+) concentration as well as in protein kinase A (PKA)-dependent protein tyrosine (Tyr) phosphorylation. Interestingly, in humans, a decrease in extracellular Ca(2+) concentration ([Ca(2+)]e) during capacitation induces an increase in Tyr phosphorylation indicating the complexity of Ca(2+) signaling during this process. In view of this, in the present study we further investigated the Ca(2+)-mediated signaling pathways implicated in Tyr phosphorylation during human sperm capacitation. Results revealed that sperm incubation in a medium without added Ca(2+) (e Ca(2+)) increased Tyr phosphorylation but did not modify PKA-mediated phosphorylation. Moreover, inhibition of either PKA or Src family kinase signaling cascades in e Ca(2+) down-regulated both PKA substrate and Tyr phosphorylations, indicating that the [Ca(2+)]e effects on Tyr phosphorylation depend on PKA targets. Inhibition of calmodulin or Ser/Thr protein phosphatase 2B also increased Tyr phosphorylation without affecting PKA-mediated phosphorylation, supporting the potential role of these Ca(2+) downstream effectors in the increase in Tyr phosphorylation observed in e Ca(2+). Experiments aimed to identify the kinase responsible for these observations revealed the presence of proline-rich tyrosine kinase 2 (PYK2), a focal adhesion kinase (FAK) family member, in human sperm, and the use of PF431396, an FAK inhibitor, supported the involvement of PYK2 in Tyr phosphorylation downstream of PKA activation. Results also showed that PYK2 was activated in e Ca(2+) as well as during capacitation and that PF431396 affected capacitated sperm motility, acrosome reaction and ability to penetrate both mouse cumulus matrix and zona-free hamster eggs. Together, our observations support PYK2 as an intermediary component of Ca(2+) signaling between PKA-mediated and Tyr phosphorylations that is required for achieving functional human sperm capacitation.
Fil: Battistone, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Alvau, A.. University of Massachussets; Estados Unidos
Fil: Salicioni, A. M.. University of Massachussets; Estados Unidos
Fil: Visconti, P. E.. University of Massachussets; Estados Unidos
Fil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Calcium
Capacitation
Human
Sperm
Tyrosine Phosphorylation
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:11336/22923
Acceder
id CONICETDig_4e46f728c9b734382981bea4e2088423
oai_identifier_str oai:ri.conicet.gov.ar:11336/22923
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitationBattistone, Maria AgustinaAlvau, A.Salicioni, A. M.Visconti, P. E.Da Ros, Vanina GabrielaCuasnicu, Patricia SaraCalciumCapacitationHumanSpermTyrosine Phosphorylationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Sperm capacitation involves an increase in intracellular Ca(2+) concentration as well as in protein kinase A (PKA)-dependent protein tyrosine (Tyr) phosphorylation. Interestingly, in humans, a decrease in extracellular Ca(2+) concentration ([Ca(2+)]e) during capacitation induces an increase in Tyr phosphorylation indicating the complexity of Ca(2+) signaling during this process. In view of this, in the present study we further investigated the Ca(2+)-mediated signaling pathways implicated in Tyr phosphorylation during human sperm capacitation. Results revealed that sperm incubation in a medium without added Ca(2+) (e Ca(2+)) increased Tyr phosphorylation but did not modify PKA-mediated phosphorylation. Moreover, inhibition of either PKA or Src family kinase signaling cascades in e Ca(2+) down-regulated both PKA substrate and Tyr phosphorylations, indicating that the [Ca(2+)]e effects on Tyr phosphorylation depend on PKA targets. Inhibition of calmodulin or Ser/Thr protein phosphatase 2B also increased Tyr phosphorylation without affecting PKA-mediated phosphorylation, supporting the potential role of these Ca(2+) downstream effectors in the increase in Tyr phosphorylation observed in e Ca(2+). Experiments aimed to identify the kinase responsible for these observations revealed the presence of proline-rich tyrosine kinase 2 (PYK2), a focal adhesion kinase (FAK) family member, in human sperm, and the use of PF431396, an FAK inhibitor, supported the involvement of PYK2 in Tyr phosphorylation downstream of PKA activation. Results also showed that PYK2 was activated in e Ca(2+) as well as during capacitation and that PF431396 affected capacitated sperm motility, acrosome reaction and ability to penetrate both mouse cumulus matrix and zona-free hamster eggs. Together, our observations support PYK2 as an intermediary component of Ca(2+) signaling between PKA-mediated and Tyr phosphorylations that is required for achieving functional human sperm capacitation.Fil: Battistone, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Alvau, A.. University of Massachussets; Estados UnidosFil: Salicioni, A. M.. University of Massachussets; Estados UnidosFil: Visconti, P. E.. University of Massachussets; Estados UnidosFil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaOxford University Press2014-09-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/22923Battistone, Maria Agustina; Alvau, A.; Salicioni, A. M.; Visconti, P. E.; Da Ros, Vanina Gabriela; et al.; Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation; Oxford University Press; Molecular Human Reproduction; 20; 11; 1-9-2014; 1054-10661360-99471460-2407CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/molehr/article-lookup/doi/10.1093/molehr/gau073info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209883/info:eu-repo/semantics/altIdentifier/doi/10.1093/molehr/gau073info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:17:17Zoai:ri.conicet.gov.ar:11336/22923instacron: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 10:17:18.28CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
title Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
spellingShingle Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
Battistone, Maria Agustina
Calcium
Capacitation
Human
Sperm
Tyrosine Phosphorylation
title_short Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
title_full Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
title_fullStr Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
title_full_unstemmed Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
title_sort Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation
dc.creator.none.fl_str_mv Battistone, Maria Agustina
Alvau, A.
Salicioni, A. M.
Visconti, P. E.
Da Ros, Vanina Gabriela
Cuasnicu, Patricia Sara
author Battistone, Maria Agustina
author_facet Battistone, Maria Agustina
Alvau, A.
Salicioni, A. M.
Visconti, P. E.
Da Ros, Vanina Gabriela
Cuasnicu, Patricia Sara
author_role author
author2 Alvau, A.
Salicioni, A. M.
Visconti, P. E.
Da Ros, Vanina Gabriela
Cuasnicu, Patricia Sara
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Calcium
Capacitation
Human
Sperm
Tyrosine Phosphorylation
topic Calcium
Capacitation
Human
Sperm
Tyrosine Phosphorylation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Sperm capacitation involves an increase in intracellular Ca(2+) concentration as well as in protein kinase A (PKA)-dependent protein tyrosine (Tyr) phosphorylation. Interestingly, in humans, a decrease in extracellular Ca(2+) concentration ([Ca(2+)]e) during capacitation induces an increase in Tyr phosphorylation indicating the complexity of Ca(2+) signaling during this process. In view of this, in the present study we further investigated the Ca(2+)-mediated signaling pathways implicated in Tyr phosphorylation during human sperm capacitation. Results revealed that sperm incubation in a medium without added Ca(2+) (e Ca(2+)) increased Tyr phosphorylation but did not modify PKA-mediated phosphorylation. Moreover, inhibition of either PKA or Src family kinase signaling cascades in e Ca(2+) down-regulated both PKA substrate and Tyr phosphorylations, indicating that the [Ca(2+)]e effects on Tyr phosphorylation depend on PKA targets. Inhibition of calmodulin or Ser/Thr protein phosphatase 2B also increased Tyr phosphorylation without affecting PKA-mediated phosphorylation, supporting the potential role of these Ca(2+) downstream effectors in the increase in Tyr phosphorylation observed in e Ca(2+). Experiments aimed to identify the kinase responsible for these observations revealed the presence of proline-rich tyrosine kinase 2 (PYK2), a focal adhesion kinase (FAK) family member, in human sperm, and the use of PF431396, an FAK inhibitor, supported the involvement of PYK2 in Tyr phosphorylation downstream of PKA activation. Results also showed that PYK2 was activated in e Ca(2+) as well as during capacitation and that PF431396 affected capacitated sperm motility, acrosome reaction and ability to penetrate both mouse cumulus matrix and zona-free hamster eggs. Together, our observations support PYK2 as an intermediary component of Ca(2+) signaling between PKA-mediated and Tyr phosphorylations that is required for achieving functional human sperm capacitation.
Fil: Battistone, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Alvau, A.. University of Massachussets; Estados Unidos
Fil: Salicioni, A. M.. University of Massachussets; Estados Unidos
Fil: Visconti, P. E.. University of Massachussets; Estados Unidos
Fil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Sperm capacitation involves an increase in intracellular Ca(2+) concentration as well as in protein kinase A (PKA)-dependent protein tyrosine (Tyr) phosphorylation. Interestingly, in humans, a decrease in extracellular Ca(2+) concentration ([Ca(2+)]e) during capacitation induces an increase in Tyr phosphorylation indicating the complexity of Ca(2+) signaling during this process. In view of this, in the present study we further investigated the Ca(2+)-mediated signaling pathways implicated in Tyr phosphorylation during human sperm capacitation. Results revealed that sperm incubation in a medium without added Ca(2+) (e Ca(2+)) increased Tyr phosphorylation but did not modify PKA-mediated phosphorylation. Moreover, inhibition of either PKA or Src family kinase signaling cascades in e Ca(2+) down-regulated both PKA substrate and Tyr phosphorylations, indicating that the [Ca(2+)]e effects on Tyr phosphorylation depend on PKA targets. Inhibition of calmodulin or Ser/Thr protein phosphatase 2B also increased Tyr phosphorylation without affecting PKA-mediated phosphorylation, supporting the potential role of these Ca(2+) downstream effectors in the increase in Tyr phosphorylation observed in e Ca(2+). Experiments aimed to identify the kinase responsible for these observations revealed the presence of proline-rich tyrosine kinase 2 (PYK2), a focal adhesion kinase (FAK) family member, in human sperm, and the use of PF431396, an FAK inhibitor, supported the involvement of PYK2 in Tyr phosphorylation downstream of PKA activation. Results also showed that PYK2 was activated in e Ca(2+) as well as during capacitation and that PF431396 affected capacitated sperm motility, acrosome reaction and ability to penetrate both mouse cumulus matrix and zona-free hamster eggs. Together, our observations support PYK2 as an intermediary component of Ca(2+) signaling between PKA-mediated and Tyr phosphorylations that is required for achieving functional human sperm capacitation.
publishDate 2014
dc.date.none.fl_str_mv 2014-09-01
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/11336/22923
Battistone, Maria Agustina; Alvau, A.; Salicioni, A. M.; Visconti, P. E.; Da Ros, Vanina Gabriela; et al.; Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation; Oxford University Press; Molecular Human Reproduction; 20; 11; 1-9-2014; 1054-1066
1360-9947
1460-2407
CONICET Digital
CONICET
url http://hdl.handle.net/11336/22923
identifier_str_mv Battistone, Maria Agustina; Alvau, A.; Salicioni, A. M.; Visconti, P. E.; Da Ros, Vanina Gabriela; et al.; Evidence for the involvement of Proline-rich Tyrosine Kinase 2 (PYK2) in tyrosine phosphorylation downstream of PKA activation during human sperm capacitation; Oxford University Press; Molecular Human Reproduction; 20; 11; 1-9-2014; 1054-1066
1360-9947
1460-2407
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/molehr/article-lookup/doi/10.1093/molehr/gau073
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209883/
info:eu-repo/semantics/altIdentifier/doi/10.1093/molehr/gau073
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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