Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.

FcepsilonRI signaling in rat basophilic leukemia cells depends on phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase Rac. Here, we studied the functional relationship among PI3-kinase, its effector protein kinase B (PKB), and Rac using inhibitors of PI3-kinase and toxins inhibiting Rac....

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Detalhes bibliográficos
Autores: Djouder, Nabil, Schmidt, G, Frings, M, Cavalié, A, Thelen, M, Aktories, K
Formato: artículo
Fecha de publicación:2001
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17540
Acesso em linha:http://hdl.handle.net/20.500.12105/17540
Access Level:acceso abierto
Palavra-chave:Animals
Biological Transport, Active
Calcium Signaling
Cell Degranulation
Cell Membrane
Cytoskeleton
Humans
Inositol Phosphates
Mast Cells
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Phosphorylation
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Rats
Receptors, IgE
Serine
Signal Transduction
Tumor Cells, Cultured
rho GTP-Binding Proteins
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/17540
network_acronym_str ES
network_name_str España
repository_id_str
spelling Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.Djouder, NabilSchmidt, GFrings, MCavalié, AThelen, MAktories, KAnimalsBiological Transport, ActiveCalcium SignalingCell DegranulationCell MembraneCytoskeletonHumansInositol PhosphatesMast CellsMitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesPhosphorylationProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRatsReceptors, IgESerineSignal TransductionTumor Cells, Culturedrho GTP-Binding ProteinsFcepsilonRI signaling in rat basophilic leukemia cells depends on phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase Rac. Here, we studied the functional relationship among PI3-kinase, its effector protein kinase B (PKB), and Rac using inhibitors of PI3-kinase and toxins inhibiting Rac. Wortmannin, an inhibitor of PI3-kinase, blocked FcepsilonRI-mediated tyrosine phosphorylation of phospholipase Cgamma, inositol phosphate formation, calcium mobilization, and secretion of hexosaminidase. Similarly, Clostridium difficile toxin B, which inactivates all Rho GTPases including Rho, Rac and Cdc42, and Clostridium sordellii lethal toxin, which inhibits Rac (possibly Cdc42) but not Rho, blocked these responses. Stimulation of the FcepsilonRI receptor induced a rapid increase in the GTP-bound form of Rac. Whereas toxin B inhibited the Rac activation, PI3-kinase inhibitors (wortmannin and LY294002) had no effect on activation of Rac. In line with this, wortmannin had no effect on tyrosine phosphorylation of the guanine nucleotide exchange factor Vav. Wortmannin, toxin B, and lethal toxin inhibited phosphorylation of PKB on Ser(473). Similarly, translocation of the pleckstrin homology domain of PKB tagged with the green fluorescent protein to the membrane, which was induced by activation of the FcepsilonRI receptor, was blocked by inhibitors of PI3-kinase and Rac inactivation. Our results indicate that in rat basophilic leukemia cells Rac and PI3-kinase regulate PKB and suggest that Rac is functionally located upstream and/or parallel of PI3-kinase/PKB in FcepsilonRI signaling.American Association of Immunologists (AAI)20242024-02-0820012001-02-0120012001-02-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/17540reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/175402026-06-12T12:43:37Z
dc.title.none.fl_str_mv Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
title Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
spellingShingle Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
Djouder, Nabil
Animals
Biological Transport, Active
Calcium Signaling
Cell Degranulation
Cell Membrane
Cytoskeleton
Humans
Inositol Phosphates
Mast Cells
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Phosphorylation
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Rats
Receptors, IgE
Serine
Signal Transduction
Tumor Cells, Cultured
rho GTP-Binding Proteins
title_short Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
title_full Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
title_fullStr Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
title_full_unstemmed Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
title_sort Rac and phosphatidylinositol 3-kinase regulate the protein kinase B in Fc epsilon RI signaling in RBL 2H3 mast cells.
dc.creator.none.fl_str_mv Djouder, Nabil
Schmidt, G
Frings, M
Cavalié, A
Thelen, M
Aktories, K
author Djouder, Nabil
author_facet Djouder, Nabil
Schmidt, G
Frings, M
Cavalié, A
Thelen, M
Aktories, K
author_role author
author2 Schmidt, G
Frings, M
Cavalié, A
Thelen, M
Aktories, K
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Animals
Biological Transport, Active
Calcium Signaling
Cell Degranulation
Cell Membrane
Cytoskeleton
Humans
Inositol Phosphates
Mast Cells
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Phosphorylation
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Rats
Receptors, IgE
Serine
Signal Transduction
Tumor Cells, Cultured
rho GTP-Binding Proteins
topic Animals
Biological Transport, Active
Calcium Signaling
Cell Degranulation
Cell Membrane
Cytoskeleton
Humans
Inositol Phosphates
Mast Cells
Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Phosphorylation
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Rats
Receptors, IgE
Serine
Signal Transduction
Tumor Cells, Cultured
rho GTP-Binding Proteins
description FcepsilonRI signaling in rat basophilic leukemia cells depends on phosphatidylinositol 3-kinase (PI3-kinase) and the small GTPase Rac. Here, we studied the functional relationship among PI3-kinase, its effector protein kinase B (PKB), and Rac using inhibitors of PI3-kinase and toxins inhibiting Rac. Wortmannin, an inhibitor of PI3-kinase, blocked FcepsilonRI-mediated tyrosine phosphorylation of phospholipase Cgamma, inositol phosphate formation, calcium mobilization, and secretion of hexosaminidase. Similarly, Clostridium difficile toxin B, which inactivates all Rho GTPases including Rho, Rac and Cdc42, and Clostridium sordellii lethal toxin, which inhibits Rac (possibly Cdc42) but not Rho, blocked these responses. Stimulation of the FcepsilonRI receptor induced a rapid increase in the GTP-bound form of Rac. Whereas toxin B inhibited the Rac activation, PI3-kinase inhibitors (wortmannin and LY294002) had no effect on activation of Rac. In line with this, wortmannin had no effect on tyrosine phosphorylation of the guanine nucleotide exchange factor Vav. Wortmannin, toxin B, and lethal toxin inhibited phosphorylation of PKB on Ser(473). Similarly, translocation of the pleckstrin homology domain of PKB tagged with the green fluorescent protein to the membrane, which was induced by activation of the FcepsilonRI receptor, was blocked by inhibitors of PI3-kinase and Rac inactivation. Our results indicate that in rat basophilic leukemia cells Rac and PI3-kinase regulate PKB and suggest that Rac is functionally located upstream and/or parallel of PI3-kinase/PKB in FcepsilonRI signaling.
publishDate 2001
dc.date.none.fl_str_mv 2001
2001-02-01
2001
2001-02-01
2024
2024-02-08
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17540
url http://hdl.handle.net/20.500.12105/17540
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Association of Immunologists (AAI)
publisher.none.fl_str_mv American Association of Immunologists (AAI)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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