Abstract:
:Rat liver membrane adenylate cyclase (EC 4.6.1.1) that has been stimulated more than 10-fold by cholera toxin (choleragen) has a 3-fold greater sensitivity to stimulation by glucagon. Choleragen similarly increases the sensitivity of cyclase to other peptide (ACTH, vasoactive intestinal polypeptide) and nonpeptide (catecholamines) hormones in this and other tissues. The rate of 125I-labeled glucagon-membrane dissociation is decreased about 2-fold in toxin-treated liver membranes. Toxin-activated cyclase activity of fat cell membranes is retained upon solubilization with Lubrol PX. Provided 125I-labeled choleragen is first incubated with cells under conditions resulting in enzyme activation, the solubilized cyclase activity migrates with a component of 125I-labeled choleragen on gel filtration chromatography. Agarose derivatives containing the "active" subunit (molecular weight 36,000) of the toxin can specifically adsorb solubilized adenylate cyclase. Toxin-stimulated cyclase can be immunoprecipitated with antitoxin or anti-"active" subunit antibodies. There is a large excess of membrane receptors (ganglioside GM1) which, with the use of choleragenoid, can be shown to be functionally equivalent with respect to cyclase activation. Choleragenoid, an inactive competitive antagonist of toxin binding, can occupy and block a large proportion of toxin receptors without affecting toxin activity. A scheme of toxin action is proposed that involves lateral membrane diffusion of the initially inactive toxin-receptor complex with subsequent direct interaction with and modulation of adenylate cyclase. The basic features of this scheme may be pertinent to the mechanisms by which hormone receptors normally modulate adenylate cyclase.
journal_name
Proc Natl Acad Sci U S Aauthors
Bennett V,O'Keefe E,Cuatrecasaş Pdoi
10.1073/pnas.72.1.33keywords:
subject
Has Abstractpub_date
1975-01-01 00:00:00pages
33-7issue
1eissn
0027-8424issn
1091-6490journal_volume
72pub_type
杂志文章abstract::Certain Escherichia coli mutants defective in phosphatidylglycerol biosynthesis accumulate two novel glycolipids, designated X and Y. Lipid X is a diacylglucosamine 1-phosphate bearing beta-hydroxymyristoyl groups at positions 2 and 3, and lipid Y has the same structure as X, except for the additional presence of a pa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.82.2.282
更新日期:1985-01-01 00:00:00
abstract::The liver plays a critical role in inducing systemic immune tolerance, for example, during limiting hypersensitivity to food allergy and in rendering acceptance of allotransplant or even hepatotropic pathogens. We investigated the unknown mechanisms of liver tolerance by using an established hepatitis B virus (HBV)-ca...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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abstract::The notion that tRNA and 5S rRNA interact through evolutionarily conserved complementary sequences has been tested by nucleolytic modification of the 5S rRNA, using the modified rRNA to reconstitute the large ribosomal subunit, and assaying for poly(uridylic acid)-directed polyphenylalanine synthesis. The 5S rRNA sequ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1982-01-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.4.1357
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.71.9.3460
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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pub_type: 杂志文章
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abstract::Three classes of heterogeneous nuclear RNA (HnRNA) alpha, beta, and gamma, with different chemical and physical properties, can be identified in the early sea urchin embryo by hybridization with poly(U). The relative amounts of these classes vary as a function of embryonic development. It is demonstrated here that the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.6.2217
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1997-12-23 00:00:00
abstract::Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition--an established endophenotype of schizophrenia. We therefore investigated whe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,多中心研究
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更新日期:2012-04-17 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.9.3410
更新日期:1990-05-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-06-28 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.072651899
更新日期:2002-04-02 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::A target protein for nalidixic and oxolinic acids in Escherichia coli, the nalA gene product (Pnal), was purified to homogeneity as judged by gel electrophoresis, using an in vitro complementation assay. It is a dimer of identical 110,000-dalton subunits. A polypeptide of this molecular weight is uniquely induced by a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.11.4767
更新日期:1977-11-01 00:00:00