Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor

The importance of the carboxyl-terminal domain of the epidermal growth factor (EGF) receptor and its five autophosphorylation sites in the in vivo interaction and tyrosine phosphorylation of the ras GTPase-activating protein (rasGAP) has been investigated, using NIH 3T3 cells transfected with mutant...

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Autores: Soler Prat, Concepció, Beguinot, Laura, Sorkin, Alexander, Carpenter, Graham
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1993
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/177648
Acceso en línea:https://hdl.handle.net/2445/177648
Access Level:acceso abierto
Palabra clave:Proteïnes
Proteïna-tirosina-fosfatasa
Metabolisme
Proteins
Protein-tyrosine phosphatase
Metabolism
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spelling Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptorSoler Prat, ConcepcióBeguinot, LauraSorkin, AlexanderCarpenter, GrahamProteïnesProteïna-tirosina-fosfatasaMetabolismeProteinsProtein-tyrosine phosphataseMetabolismThe importance of the carboxyl-terminal domain of the epidermal growth factor (EGF) receptor and its five autophosphorylation sites in the in vivo interaction and tyrosine phosphorylation of the ras GTPase-activating protein (rasGAP) has been investigated, using NIH 3T3 cells transfected with mutant EGF receptors. Phosphorylation of rasGAP by EGF receptor mutants, in which one to four autophosphorylation sites (Tyr-1173, -1148, -1086, and -1068) were mutated to phenylalanine, was reduced by 50-60% compared to the wild-type receptor. Elimination of these four autophosphorylation sites by truncation of 123 carboxyl-terminal residues of the EGF receptor paralleled results obtained with point mutants. Substantial inhibition (about 90%) of rasGAP tyrosine phosphorylation by the EGF receptor occurred only when the remaining autophosphorylation site (Tyr-992) was mutated, in the context of this truncated receptor or in the full-length receptor mutated at all four other autophosphorylation sites. However, a point mutation of only Tyr-992 in the full-length receptor suppressed tyrosine phosphorylation of rasGAP only by 50%. In contrast, an EGF receptor lacking the last 214 amino acid residues (Dc214), which encompasses all five autophosphorylation sites, phosphorylated rasGAP to the same extent as the wild-type receptor. However, this truncated receptor was significantly impaired in its capacity to phosphorylate phospholipase C-gamma 1. Interestingly, while EGF receptor autophosphorylation sites are required for EGF-induced rasGAP association with the receptor, maximal phosphorylation of rasGAP by the truncated receptor Dc214 occurred without detectable formation of receptor-rasGAP complexes. Furthermore, the capacity of mutated EGF receptors to bring about focal transformation was correlated with their capacity to phosphorylate rasGAP.American Society for Biochemistry and Molecular Biology1993info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/177648Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://www.jbc.org/issue/S0021-9258(20)X6719-6Journal of Biological Chemistry, 1993, vol. 268, num. 29, p. 22010-22019(c) American Society for Biochemistry and Molecular Biology, 1993info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1776482026-05-27T06:46:51Z
dc.title.none.fl_str_mv Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
title Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
spellingShingle Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
Soler Prat, Concepció
Proteïnes
Proteïna-tirosina-fosfatasa
Metabolisme
Proteins
Protein-tyrosine phosphatase
Metabolism
title_short Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
title_full Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
title_fullStr Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
title_full_unstemmed Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
title_sort Tyrosine phosphorylation of ras GTPase activating protein does not require association with the epidermal growth factor receptor
dc.creator.none.fl_str_mv Soler Prat, Concepció
Beguinot, Laura
Sorkin, Alexander
Carpenter, Graham
author Soler Prat, Concepció
author_facet Soler Prat, Concepció
Beguinot, Laura
Sorkin, Alexander
Carpenter, Graham
author_role author
author2 Beguinot, Laura
Sorkin, Alexander
Carpenter, Graham
author2_role author
author
author
dc.subject.none.fl_str_mv Proteïnes
Proteïna-tirosina-fosfatasa
Metabolisme
Proteins
Protein-tyrosine phosphatase
Metabolism
topic Proteïnes
Proteïna-tirosina-fosfatasa
Metabolisme
Proteins
Protein-tyrosine phosphatase
Metabolism
description The importance of the carboxyl-terminal domain of the epidermal growth factor (EGF) receptor and its five autophosphorylation sites in the in vivo interaction and tyrosine phosphorylation of the ras GTPase-activating protein (rasGAP) has been investigated, using NIH 3T3 cells transfected with mutant EGF receptors. Phosphorylation of rasGAP by EGF receptor mutants, in which one to four autophosphorylation sites (Tyr-1173, -1148, -1086, and -1068) were mutated to phenylalanine, was reduced by 50-60% compared to the wild-type receptor. Elimination of these four autophosphorylation sites by truncation of 123 carboxyl-terminal residues of the EGF receptor paralleled results obtained with point mutants. Substantial inhibition (about 90%) of rasGAP tyrosine phosphorylation by the EGF receptor occurred only when the remaining autophosphorylation site (Tyr-992) was mutated, in the context of this truncated receptor or in the full-length receptor mutated at all four other autophosphorylation sites. However, a point mutation of only Tyr-992 in the full-length receptor suppressed tyrosine phosphorylation of rasGAP only by 50%. In contrast, an EGF receptor lacking the last 214 amino acid residues (Dc214), which encompasses all five autophosphorylation sites, phosphorylated rasGAP to the same extent as the wild-type receptor. However, this truncated receptor was significantly impaired in its capacity to phosphorylate phospholipase C-gamma 1. Interestingly, while EGF receptor autophosphorylation sites are required for EGF-induced rasGAP association with the receptor, maximal phosphorylation of rasGAP by the truncated receptor Dc214 occurred without detectable formation of receptor-rasGAP complexes. Furthermore, the capacity of mutated EGF receptors to bring about focal transformation was correlated with their capacity to phosphorylate rasGAP.
publishDate 1993
dc.date.none.fl_str_mv 1993
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177648
url https://hdl.handle.net/2445/177648
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://www.jbc.org/issue/S0021-9258(20)X6719-6
Journal of Biological Chemistry, 1993, vol. 268, num. 29, p. 22010-22019
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 1993
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 1993
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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