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[PMID]:28582432
[Au] Autor:Wang J; Chandrasekhar V; Abbadessa G; Yu Y; Schwartz B; Kontaridis MI
[Ad] Endereço:Department of Medicine, Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
[Ti] Título:In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy.
[So] Source:PLoS One;12(6):e0178905, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Noonan Syndrome with Multiple Lentigines (NSML, formerly LEOPARD syndrome) is an autosomal dominant "RASopathy" disorder manifesting in congenital heart disease. Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. We previously generated knock-in mice harboring the PTPN11 mutation Y279C, one of the most common NSML alleles; these now-termed SHP2Y279C/+ mice recapitulate the human disorder and develop hypertrophic cardiomyopathy (HCM) by 12 weeks of age. Functionally, heart and/or cardiomyocyte lysates from SHP2Y279C/+ mice exhibit increased basal and agonist-induced AKT and mTOR activities. Here, we sought to determine whether we could reverse the hypertrophy in SHP2Y279C/+ mice using ARQ 092, an oral and selective allosteric AKT inhibitor currently in clinical trials for patients with PI3K/AKT-driven tumors or Proteus syndrome. We obtained echocardiographs of SHP2Y279C/+ and wildtype (SHP2+/+) littermates, either in the presence or absence of ARQ 092 at 12, 14, and 16 weeks of age. While SHP2Y279C/+ mice developed significant left ventricular hypertrophy by 12 weeks, as indicated by decreased chamber dimension and increased posterior wall thickness, treatment of SHP2Y279C/+ mice with ARQ 092 normalized the hypertrophy in as early as 2 weeks following treatment, with hearts comparable in size to those in wildtype (SHP2+/+) mice. In addition, we observed an increase in fractional shortening (FS%) in SHP2Y279C/+ mice, an effect of increased compensatory hypertrophy, which was not apparent in SHP2Y279C/+ mice treated with ARQ 092, suggesting functional improvement of HCM upon treatment with the AKT inhibitor. Finally, we found that ARQ 092 specifically inhibited AKT activity, as well as its downstream effectors, PRAS and S6RP in NSML mice. Taken together, these data suggest ARQ 092 may be a promising novel therapy for treatment of hypertrophy in NSML patients.
[Mh] Termos MeSH primário: Aminopiridinas/farmacologia
Cardiomiopatia Hipertrófica/tratamento farmacológico
Cardiotônicos/farmacologia
Imidazóis/farmacologia
Síndrome LEOPARD/tratamento farmacológico
Inibidores de Proteínas Quinases/farmacologia
Proteína Tirosina Fosfatase não Receptora Tipo 11/genética
Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores
[Mh] Termos MeSH secundário: Alelos
Animais
Cardiomiopatia Hipertrófica/diagnóstico por imagem
Cardiomiopatia Hipertrófica/genética
Cardiomiopatia Hipertrófica/metabolismo
Modelos Animais de Doenças
Ecocardiografia
Regulação da Expressão Gênica
Seres Humanos
Síndrome LEOPARD/diagnóstico por imagem
Síndrome LEOPARD/genética
Síndrome LEOPARD/metabolismo
Masculino
Camundongos
Camundongos Transgênicos
Mutação
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/metabolismo
Miócitos Cardíacos/patologia
Fosfoproteínas/antagonistas & inibidores
Fosfoproteínas/genética
Fosfoproteínas/metabolismo
Domínios Proteicos
Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
Proteínas Proto-Oncogênicas c-akt/genética
Proteínas Proto-Oncogênicas c-akt/metabolismo
Transdução de Sinais
Serina-Treonina Quinases TOR/genética
Serina-Treonina Quinases TOR/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ARQ 092); 0 (Aminopyridines); 0 (Cardiotonic Agents); 0 (Imidazoles); 0 (Phosphoproteins); 0 (Protein Kinase Inhibitors); 0 (proline-rich Akt substrate, 40 kDa protein, mouse); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.1.1 (mTOR protein, mouse); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11); EC 3.1.3.48 (Ptpn11 protein, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178905


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[PMID]:28483241
[Au] Autor:van Nierop JWI; van Trier DC; van der Burgt I; Draaisma JMT; Mylanus EAM; Snik AF; Admiraal RJC; Kunst HPM
[Ad] Endereço:Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Josephine.vannierop@radboudumc.nl.
[Ti] Título:Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11.
[So] Source:Int J Pediatr Otorhinolaryngol;97:228-234, 2017 Jun.
[Is] ISSN:1872-8464
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). The present study describes four NS patients and one NSML patient with a PTPN11 mutation. They all had severe to profound hearing loss, and they received a CI. The age at which the CI surgery occurred ranged from 1 to 13 years old, and the audiological results in all five patients improved after the CI. Otological and audiological examinations in NS and NSML are important, and for those with severe hearing loss, the CI surgery improved the audiological outcome regardless of age.
[Mh] Termos MeSH primário: Implante Coclear/métodos
Perda Auditiva/cirurgia
Síndrome LEOPARD/terapia
Síndrome de Noonan/terapia
Proteína Tirosina Fosfatase não Receptora Tipo 11/genética
[Mh] Termos MeSH secundário: Adolescente
Audiometria
Criança
Pré-Escolar
Feminino
Seres Humanos
Lactente
Síndrome LEOPARD/genética
Masculino
Mutação
Síndrome de Noonan/diagnóstico
Síndrome de Noonan/genética
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.1.3.48 (PTPN11 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE


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Taitson, Paulo Franco
Texto completo SciELO Brasil
[PMID]:28225973
[Au] Autor:Cançado FH; Silva LC; Taitson PF; Andrade AC; Pithon MM; Oliveira DD
[Ad] Endereço:Odontology Department of the Pontifícia Universidade Católica de Minas Gerais (PUC Minas) - Belo Horizonte (MG), Brazil.
[Ti] Título:Do you know this syndrome? Leopard syndrome.
[So] Source:An Bras Dermatol;92(1):127-129, 2017 Jan-Feb.
[Is] ISSN:1806-4841
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Hypertrophic cardiomyopathy is known as Leopard syndrome, which is a mnemonic rule for multiple lentigines (L), electrocardiographic conduction abnormalities (E), ocular hypertelorism (O), pulmonary stenosis (P), abnormalities of genitalia (A), retardation of growth (R), and deafness (D). We report the case of a 12-year-old patient with some of the abovementioned characteristics: hypertelorism, macroglossia, lentigines, hypospadias, cryptorchidism, subaortic stenosis, growth retardation, and hearing impairment. Due to this set of symptoms, we diagnosed Leopard syndrome.
[Mh] Termos MeSH primário: Síndrome LEOPARD/diagnóstico
[Mh] Termos MeSH secundário: Criança
Seres Humanos
Masculino
Fenótipo
[Pt] Tipo de publicação:CASE REPORTS
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170223
[St] Status:MEDLINE


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[PMID]:28069640
[Au] Autor:Falik-Zaccai TC; Barsheshet Y; Mandel H; Segev M; Lorber A; Gelberg S; Kalfon L; Ben Haroush S; Shalata A; Gelernter-Yaniv L; Chaim S; Raviv Shay D; Khayat M; Werbner M; Levi I; Shoval Y; Tal G; Shalev S; Reuveni E; Avitan-Hersh E; Vlodavsky E; Appl-Sarid L; Goldsher D; Bergman R; Segal Z; Bitterman-Deutsch O; Avni O
[Ad] Endereço:Institute of Human Genetics, Galilee Medical Center, Nahariya, Israel falikmd.genetics@gmail.com orly.avni@biu.ac.il.
[Ti] Título:Sequence variation in results in a novel form of cardio-cutaneous syndrome.
[So] Source:EMBO Mol Med;9(3):319-336, 2017 Mar.
[Is] ISSN:1757-4684
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at  encoding the iASPP protein was identified in three infants and in the mother of the other two. Patients' fibroblasts and -knocked down human fibroblasts presented higher expression levels of pro-inflammatory cytokine genes in response to lipopolysaccharide, as well as -knocked down murine cardiomyocytes and hearts of -deficient mice. The hypersensitivity to lipopolysaccharide was NF-κB-dependent, and its inducible binding activity to promoters of pro-inflammatory cytokine genes was elevated in patients' fibroblasts. RNA sequencing of -knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in -deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined  as the gene underlying a novel autosomal-recessive cardio-cutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors.
[Mh] Termos MeSH primário: Códon sem Sentido
Peptídeos e Proteínas de Sinalização Intracelular/genética
Síndrome LEOPARD/genética
Síndrome LEOPARD/patologia
Proteínas Repressoras/genética
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Pré-Escolar
Citocinas/secreção
Feminino
Fibroblastos/metabolismo
Técnicas de Silenciamento de Genes
Seres Humanos
Lactente
Lipopolissacarídeos/toxicidade
Masculino
Camundongos
Camundongos Knockout
Miócitos Cardíacos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Nonsense); 0 (Cytokines); 0 (Intracellular Signaling Peptides and Proteins); 0 (Lipopolysaccharides); 0 (PPP1R13L protein, human); 0 (Ppp1r13l protein, mouse); 0 (Repressor Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170111
[St] Status:MEDLINE
[do] DOI:10.15252/emmm.201606523


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[PMID]:27840890
[Au] Autor:Wang J; Zhang J; Li X; Wang Z; Lei D; Wang G; Li J; Zhang S; Li Z; Li M
[Ad] Endereço:Department of Dermatology, Henan Provincial People's Hospital, No.7 Weiwu Road, Zhengzhou 450003, China.
[Ti] Título:A Novel De novo Mutation of the SASH1 Gene in a Chinese Family with Multiple Lentigines.
[So] Source:Acta Derm Venereol;97(4):530-531, 2017 04 06.
[Is] ISSN:1651-2057
[Cp] País de publicação:Sweden
[La] Idioma:eng
[Mh] Termos MeSH primário: Síndrome LEOPARD/genética
Mutação de Sentido Incorreto
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Adulto
Grupo com Ancestrais do Continente Asiático/genética
Análise Mutacional de DNA
Feminino
Predisposição Genética para Doença
Hereditariedade
Heterozigoto
Seres Humanos
Síndrome LEOPARD/diagnóstico
Síndrome LEOPARD/etnologia
Síndrome LEOPARD/radioterapia
Lasers de Estado Sólido/uso terapêutico
Terapia com Luz de Baixa Intensidade/instrumentação
Masculino
Linhagem
Fenótipo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (SASH1 protein, human); 0 (Tumor Suppressor Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161115
[St] Status:MEDLINE
[do] DOI:10.2340/00015555-2575


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[PMID]:27729118
[Au] Autor:Vermeire K; Wexler L; Vambutas A
[Ad] Endereço:Dept of Otolaryngology, Long Island Jewish Medical Center, NY, USA. Electronic address: Kmv1@nyu.edu.
[Ti] Título:The experience of bilateral cochlear implantation in a child with LEOPARD syndrome.
[So] Source:Int J Pediatr Otorhinolaryngol;90:125-127, 2016 Nov.
[Is] ISSN:1872-8464
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:We present a 3-year old boy with Leopard syndrome. His clinical manifestations included a congenital bilateral sensorineural hearing loss. He underwent cochlear implantation on the right side at age 1 year and on the left side at age 1.5 years. The patient is doing very well and mainstreamed in a regular pre-school program with a teacher of the deaf and home based speech therapy. Bilateral cochlear implantation in the case of a child with Leopard syndrome can be successful.
[Mh] Termos MeSH primário: Implante Coclear
Perda Auditiva Bilateral/reabilitação
Perda Auditiva Neurossensorial/reabilitação
Síndrome LEOPARD/reabilitação
[Mh] Termos MeSH secundário: Pré-Escolar
Implantes Cocleares
Perda Auditiva Bilateral/etiologia
Perda Auditiva Neurossensorial/etiologia
Seres Humanos
Síndrome LEOPARD/complicações
Inclusão Educacional
Masculino
Pessoas com Deficiência Auditiva
Fala
Percepção da Fala
Fonoterapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161013
[St] Status:MEDLINE


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[PMID]:27666661
[Au] Autor:Zhang J; Li M; Yao Z
[Ad] Endereço:Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
[Ti] Título:Molecular screening strategies for NF1-like syndromes with café-au-lait macules (Review).
[So] Source:Mol Med Rep;14(5):4023-4029, 2016 Nov.
[Is] ISSN:1791-3004
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Multiple café-au-lait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. However, a group of genetic disorders presenting with CALM have mutations that are involved in human skin pigmentation regulation signaling pathways, including KIT ligand/KIT proto­oncogene receptor tyrosine kinase and Ras/mitogen­activated protein kinase. These disorders, which include Legius syndrome, Noonan syndrome with multiple lentigines or LEOPARD syndrome, and familial progressive hyperpigmentation) are difficult to distinguish from NF1 at early stages, using skin appearance alone. Furthermore, certain syndromes are clinically overlapping and molecular testing is a vital diagnostic method. The present review aims to provide an overview of these 'NF1­like' inherited diseases and recommend a cost­effective strategy for making a clear diagnosis among these diseases with an ambiguous borderline.
[Mh] Termos MeSH primário: Manchas Café com Leite/genética
Síndrome LEOPARD/genética
Neurofibromatose 1/genética
Síndrome de Noonan/genética
[Mh] Termos MeSH secundário: Manchas Café com Leite/diagnóstico
Manchas Café com Leite/patologia
Diagnóstico Diferencial
Seres Humanos
Síndrome LEOPARD/diagnóstico
Síndrome LEOPARD/patologia
Mutação
Neurofibromatose 1/diagnóstico
Neurofibromatose 1/patologia
Síndrome de Noonan/diagnóstico
Síndrome de Noonan/patologia
Patologia Molecular
Transdução de Sinais/genética
Pigmentação da Pele/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170410
[Lr] Data última revisão:
170410
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160927
[St] Status:MEDLINE
[do] DOI:10.3892/mmr.2016.5760


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[PMID]:27484170
[Au] Autor:Zhang J; Shen J; Cheng R; Ni C; Liang J; Li M; Yao Z
[Ad] Endereço:Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, P.R. China.
[Ti] Título:Identification of a PTPN11 hot spot mutation in a child with atypical LEOPARD syndrome.
[So] Source:Mol Med Rep;14(3):2639-43, 2016 Sep.
[Is] ISSN:1791-3004
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:LEOPARD syndrome (LS) is an autosomal dominant inherited disorder primarily caused by mutations in the PTPN11, RAF1 and BRAF genes. Characteristic features include lentigines, craniofacial dysmorphism, myocardium or valve abnormalities, eletrocardiographic conduction defects and deafness. LS, neurofibromatosis type 1, Noonan syndrome and Legius syndrome are a group of highly overlapped disorders termed 'RASopathies'. Therefore, clinical discrimination between these syndromes represents a huge challenge. The present study reports a young child diagnosed with LS via identification of a common p.Thr468Met mutation in PTPN11. Taking into account two Taiwanese LS cases with an identical mutation, Thr468Met is likely to be the most prevalent mutation in the Chinese population. Furthermore, this study suggests that a clinical diagnosis of LS should be considered for individuals with congenital cardiac defects and atypical lentigines (i.e., light brown freckles) scattered particularly on the face.
[Mh] Termos MeSH primário: Síndrome LEOPARD/diagnóstico
Síndrome LEOPARD/genética
Mutação
Fenótipo
Proteína Tirosina Fosfatase não Receptora Tipo 11/genética
[Mh] Termos MeSH secundário: Alelos
Pré-Escolar
Análise Mutacional de DNA
Estudos de Associação Genética
Genótipo
Seres Humanos
Masculino
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
EC 3.1.3.48 (PTPN11 protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170406
[Lr] Data última revisão:
170406
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160804
[St] Status:MEDLINE
[do] DOI:10.3892/mmr.2016.5547


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[PMID]:27238887
[Au] Autor:van den Berg H; Schreuder WH; Jongmans M; van Bommel-Slee D; Witsenburg B; de Lange J
[Ad] Endereço:Department of Pediatric Oncology, Emma Children Hospital/Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: h.vandenberg@amc.uva.nl.
[Ti] Título:Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines.
[So] Source:Eur J Med Genet;59(8):425-8, 2016 Aug.
[Is] ISSN:1878-0849
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A patient with Noonan syndrome with multiple lentigines (NSML) and multiple giant cell lesions (MGCL) in mandibles and maxillae is described. A mutation p.Thr468Met in the PTPN11-gene was found. This is the second reported NSML patient with MGCL. Our case adds to the assumption that, despite a different molecular pathogenesis and effect on the RAS/MEK pathway, NSML shares the development of MGCL, with other RASopathies.
[Mh] Termos MeSH primário: Células Gigantes/patologia
Síndrome LEOPARD/diagnóstico
[Mh] Termos MeSH secundário: Biópsia
Criança
Seres Humanos
Arcada Osseodentária/patologia
Masculino
Fenótipo
Pele/patologia
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170206
[Lr] Data última revisão:
170206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160531
[St] Status:MEDLINE


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[PMID]:26742426
[Au] Autor:Noda S; Takahashi A; Hayashi T; Tanuma S; Hatakeyama M
[Ad] Endereço:Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
[Ti] Título:Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling.
[So] Source:Biochem Biophys Res Commun;469(4):1133-9, 2016 Jan 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin.
[Mh] Termos MeSH primário: Síndrome LEOPARD/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 11/genética
Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
Proteínas Supressoras de Tumor/metabolismo
Via de Sinalização Wnt
[Mh] Termos MeSH secundário: Animais
Células COS
Catálise
Cercopithecus aethiops
Ativação Enzimática
Seres Humanos
Síndrome LEOPARD/genética
Mutação/genética
Ligação Proteica
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CDC73 protein, human); 0 (Tumor Suppressor Proteins); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:160122
[Lr] Data última revisão:
160122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160109
[St] Status:MEDLINE



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