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1.
Proc Natl Acad Sci U S A ; 98(23): 12978-83, 2001 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-11687619

RESUMO

The family of the PII signal transduction proteins contains the most highly conserved signaling proteins in nature. The cyanobacterial PII-homologue transmits signals of the cellular nitrogen status and carbon status through phosphorylation of a seryl-residue. To identify the enzyme responsible for dephosphorylation of the phosphorylated PII protein in Synechocystis PCC 6803, prospective phosphatase encoding genes were inactivated by targeted insertion of kanamycin resistance cassettes. Disruption of ORF sll1771 generates a mutant unable to dephosphorylate PII under various experimental conditions. On the basis of conserved signature motifs, the sll1771 product (termed PphA) is a member of the protein phosphatase 2C (PP2C) superfamily, which is characterized by Mg(2+)/Mn(2+)-dependent catalytic activity. Biochemical analysis of overexpressed and purified PphA confirms its PP2C-type enzymatic properties and demonstrated its reactivity toward the phosphorylated PII protein. Thus, PphA is the first protein phosphatase in Synechocystis PCC 6803 for which the physiological substrate and function is known.


Assuntos
Proteínas de Bactérias/metabolismo , Cianobactérias/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteínas de Saccharomyces cerevisiae , Sequência de Bases , Mapeamento Cromossômico , Primers do DNA , Fases de Leitura Aberta , Fosfoproteínas Fosfatases/genética , Fosforilação , Filogenia , Proteína Fosfatase 2 , Proteína Fosfatase 2C
2.
J Neurol ; 246(7): 556-61, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10463356

RESUMO

Hereditary spastic paraplegia is a group of clinically and genetically heterogeneous disorders consisting of pure and complicated forms. A variant with the additional features of severe atrophy of the small hand muscles, dysarthria, mental retardation, and short stature has been termed Troyer syndrome (MIM#275900) after the name of Old Order Amish families suffering from these symptoms. We report here an Austrian family with two individuals who exhibit all the features of Troyer syndrome, and provide additional data on this disorder. Electrophysiological studies showed chronic denervation and reduced motor nerve conduction velocities but normal sensory potentials. Muscle biopsy revealed a neurogenic pattern while the sural nerve was normal on histological examination. Brain abnormalities on magnetic resonance imaging consisted of a thin corpus callosum with a poorly developed cingulate gyrus and mild periventricular signal hyperintensities. These findings characterize the Troyer syndrome as a disorder of the first and second motor neuron with additional damage in the brain. The morphological features observed in this family may contribute to the grouping and subsequent understanding of complicated forms of hereditary spastic paraplegia, together with similar observations in other, more recently reported families.


Assuntos
Agenesia do Corpo Caloso , Doença dos Neurônios Motores/genética , Músculo Esquelético/patologia , Paraplegia Espástica Hereditária/genética , Adulto , Biópsia , Corpo Caloso/patologia , Feminino , Mãos , Humanos , Imageamento por Ressonância Magnética , Doença dos Neurônios Motores/fisiopatologia , Condução Nervosa , Linhagem , Paraplegia Espástica Hereditária/fisiopatologia , Síndrome
3.
Mol Microbiol ; 26(1): 81-90, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9383191

RESUMO

The phosphorylation state of the putative signal transduction protein P(II) from the cyanobacterium Synechococcus sp. strain PCC 7942 depends on the cellular state of nitrogen and carbon assimilation. In this study, dephosphorylation of phosphorylated P(II) protein (P[II]-P) was investigated both in vivo and in vitro. The in vivo studies implied that P(II)-P dephosphorylation is regulated by inhibitory metabolites involved in the glutamine synthetase-glutamate synthase pathway of ammonium assimilation. An in vitro assay for P(II)-P dephosphorylation was established that revealed a Mg2+-dependent P(II)-P phosphatase activity. P(II)-P phosphatase and P(II) kinase activities could be separated biochemically. A partially purified P(II)-P phosphatase preparation also catalysed the dephosphorylation of phosphoserine/phosphothreonine residues on other proteins in a Mg2+-dependent manner. However, only dephosphorylation of P(II)-P was regulated by synergistic inhibition by ATP and 2-oxoglutarate. As the same metabolites stimulate the P(II) kinase activity, it appears that the phosphorylation state of P(II) is determined by ATP and 2-oxoglutarate-dependent reciprocal reactivity of P(II) towards its phosphatase and kinase.


Assuntos
Trifosfato de Adenosina/farmacologia , Proteínas de Bactérias/metabolismo , Cianobactérias/enzimologia , Ácidos Cetoglutáricos/farmacologia , Fosfoproteínas Fosfatases/metabolismo , Western Blotting , Detergentes/farmacologia , Dicicloexilcarbodi-Imida/farmacologia , Inibidores Enzimáticos/farmacologia , Glutamato-Amônia Ligase/metabolismo , Gliceraldeído/metabolismo , Magnésio/farmacologia , Proteínas PII Reguladoras de Nitrogênio , Fosfoproteínas Fosfatases/isolamento & purificação , Fosfoproteínas/metabolismo , Fosforilação , Proteínas Quinases/metabolismo , Transdução de Sinais/fisiologia
4.
J Clin Epidemiol ; 49(1): 73-8, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8598514

RESUMO

Age and education have been found to affect the Mini Mental State Examination (MMSE) score of elderly normals, but there have been no studies assessing the influence of environmental and behavioral factors on this test. We therefore administered the MMSE to 1437 normal elderly subjects in the setting of a stroke prevention study and correlated their results to 16 sociodemographic, environmental, and behavioral factors, and vascular risk factors. Study statistics composed of a multiple logistic regression analysis and graphical models revealed the relations between variables in greater detail. Logistic regression yielded education level, occupational status, living as a single, general life stress, physical strain, and physical inactivity to be independent predictors of the MMSE score. Age was not included in this model. Graphical models demonstrated similar results, but did not include living as a single and physical inactivity. As shown in our independence graph, general life stress is the crucial predictor and links other environmental and sociodemographic variables with the test performance of elderly normals.


Assuntos
Comportamento , Transtornos Cerebrovasculares/prevenção & controle , Escalas de Graduação Psiquiátrica , Meio Social , Fatores Socioeconômicos , Idoso , Idoso de 80 Anos ou mais , Áustria/epidemiologia , Transtornos Cerebrovasculares/epidemiologia , Cognição , Gráficos por Computador , Demência/diagnóstico , Demografia , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco
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