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21.
The tyrosine kinase activity of the epidermal growth factor receptor (EGFR-TK) was determined at varying poly-Glu6Ala3Tyr1 (GAT) or [Val5]-angiotensin II (AT) and constant ATP concentrations and vice versa. With GAT as substrate, double reciprocal plots intersected practically on the abscissa following EGFR-TK pre-activation with EGF, but below the abscissa without EGF pre-activation. The EGFR-TK inhibitors App(NH)p (5'-adenylyl-beta, gamma-imidodiphosphate) and ADP were competitive with ATP and noncompetitive with GAT. Four families of 1/v vs. 1/[ATP] plots, constructed at different fixed concentrations of ADP and a different constant concentration of GAT for each family, yielded Slope1/ATP replots which intersected to the left of the ordinate and below the abscissa. GAT and AT, as cosubstrates, were competitive with each other and noncompetitive with ATP; 1/v vs. 1/[GAT] or 1/[AT] plots were hyperbolic and reached horizontal asymptotes when v was expressed as the rate of common product formation. All data were subjected to computer best-fit analysis by a program written especially for this purpose. We conclude that (i) the EGFR-TK reaction follows a Sequential Bi-Bi Rapid Equilibrium Random mechanism, and (ii) EGF induces conformational changes in the EGFR-TK active center which lead to marked decreases in the apparent dissociation constants of both substrates of the kinase reaction and a concomitant increase in initial velocities and Vmax (apparent). 相似文献
22.
The neurobiology of selective attention. 总被引:8,自引:0,他引:8
Research in the field of selective visual attention has recently seen substantial progress in several areas. Neuroimaging and electrical recording results have indicated that selective attention amplifies neural activity in prestriate areas concerned with basic visual processing. Imaging and cellular studies are delineating the networks of anatomical areas that serve as the source of attentional modulation and have suggested that these networks are anatomically distinct from the sites of the resulting amplifications. Cognitive studies of visual search have explored the role of these amplified computations in the integration of visual features into objects. Attentional effects in normal subjects, and their disruption following brain injury, have revealed the mental representations upon which attention operates. 相似文献
23.
Posner , Herbert B., and William S. Hillman . (Yale U., New Haven, Conn.) Effects of x irradiation on Lemna perpusilla. Amer. Jour. Bot. 47(6): 506–511. Illus. 1960.—The effects of x rays on the multiplication rates (MR), percent flowering (Fl%) and gross morphology of aseptically grown cultures of Lemna perpusilla, strain 6746, were studied. MR values are unaffected by doses of less than 300 r but are progressively depressed as the dose increases. The effect of a given dose on short-term MR values is the same at the 2 dosage intensities used, 500 and 2000 r/min. The inhibitory effect of intermediate doses on long-term growth is delayed; high doses have an “immediate” effect. Bleaching of fronds and cessation of growth occur in all cultures given 5,000 r or higher. Radiosensitivity is not altered by addition of yeast extract and casein hydrolysate to the medium. Depressed Fl% and seed production appear to be consequences of lowered MR. Morphological aberrations such as small size, epinasty and wrinkling are temporary. Frond-sequence may be altered by x rays but this aberration is permanent. Various aspects of the results are discussed. 相似文献
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Hyun Seok Kim Saurabh Mendiratta Jiyeon Kim Chad Victor Pecot Jill E. Larsen Iryna Zubovych Bo Yeun Seo Jimi Kim Banu Eskiocak Hannah Chung Elizabeth McMillan Sherry Wu Jef De Brabander Kakajan Komurov Jason E. Toombs Shuguang Wei Michael Peyton Noelle Williams Adi F. Gazdar Bruce A. Posner Rolf A. Brekken Anil K. Sood Ralph J. Deberardinis Michael G. Roth John D. Minna Michael A. White 《Cell》2013
27.
Abigail H. Davies Joanna McGlashan Mareike G. Posner April K. Roberts Clifford C. Shone K. Ravi Acharya 《Biochemistry and Biophysics Reports》2016
Clostridium difficile binary toxin (CDT) is an ADP-ribosyltransferase which is linked to enhanced pathogenesis of C. difficile strains. CDT has dual function: domain a (CDTa) catalyses the ADP-ribosylation of actin (enzymatic component), whereas domain b (CDTb) transports CDTa into the cytosol (transport component). Understanding the molecular mechanism of CDT is necessary to assess its role in C. difficile infection. Identifying amino acids that are essential to CDTa function may aid drug inhibitor design to control the severity of C. difficile infections. Here we report mutations of key catalytic residues within CDTa and their effect on CDT cytotoxicity. Rather than an all-or-nothing response, activity of CDTa mutants vary with the type of amino acid substitution; S345A retains cytotoxicity whereas S345Y was sufficient to render CDT non-cytotoxic. Thus CDTa cytotoxicity levels are directly linked to ADP-ribosyltransferase activity. 相似文献
28.
Heath C Posner MG Aass HC Upadhyay A Scott DJ Hough DW Danson MJ 《The FEBS journal》2007,274(20):5406-5415
The aerobic archaea possess four closely spaced, adjacent genes that encode proteins showing significant sequence identities with the bacterial and eukaryal components comprising the 2-oxoacid dehydrogenase multi-enzyme complexes. However, catalytic activities of such complexes have never been detected in the archaea, although 2-oxoacid ferredoxin oxidoreductases that catalyze the equivalent metabolic reactions are present. In the current paper, we clone and express the four genes from the thermophilic archaeon, Thermoplasma acidophilum, and demonstrate that the recombinant enzymes are active and assemble into a large (M(r) = 5 x 10(6)) multi-enzyme complex. The post-translational incorporation of lipoic acid into the transacylase component of the complex is demonstrated, as is the assembly of this enzyme into a 24-mer core to which the other components bind to give the functional multi-enzyme system. This assembled complex is shown to catalyze the oxidative decarboxylation of branched-chain 2-oxoacids and pyruvate to their corresponding acyl-CoA derivatives. Our data constitute the first proof that the archaea possess a functional 2-oxoacid dehydrogenase complex. 相似文献
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Katzburg S Hendel D Waisman A Posner GH Kaye AM Somjen D 《The Journal of steroid biochemistry and molecular biology》2004,88(2):213-219
Pretreatment with 1 nM 1,25-dihydroxyvitamin D(3) (1,25), or non-hypercalcemic Vitamin D analogs, upregulated the response of creatine kinase (CK) to 17beta-estradiol (30 nM E(2)), raloxifene (3000 nM RAL) or dihydrotestosterone (300 nM DHT) in primary human bone cells. Previously, we reported that these osteoblast-like cells responded to gonadal steroids in a sex specific manner. Bone cells derived from pre-menopausal women showed greater stimulation of CK specific activity by E(2) than bone cells from post-menopausal women; in male-derived cells no age related difference was found. In this study, we treated cells derived from female or male bones, at different ages, with the side chain modified analogs of Vitamin D: CB 1093 (CB), EB 1089 (EB), MC 1288 (MC) and the demonstrably non-calcemic hybrid analog JK 1624 F2-2 (JKF), by daily addition of 1 nM, for 3 days. On day 4, cells were incubated with sex steroids for 4h and cell extracts were prepared. Pretreatment with JKF or CB significantly upregulated the response to 30 nM E(2) in all female-derived cells and to 300 nM DHT in mature male-derived cells. In cells from older males, only JKF caused augmentation of DHT action. Bone cells from pre- or post-menopausal females responded to 3000 nM RAL by increased CK activity to the same extent as to 30 nM E(2); however, RAL and E(2), when applied together, resulted in mutual annihilation of their agonist activities. Vitamin D analogs prevented the antagonistic effect of RAL in the presence of E(2), possibly due to increased numbers of ERs. Both estrogen receptors, alpha (ERalpha) and beta (ERbeta), were expressed in male- as well as in female-derived cells. However, only in female-derived cells were ERalpha and ERbeta upregulated by pretreatment with Vitamin D analogs. This study raises the possibility of testing combined Vitamin D analog and estrogen replacement treatment for post-menopausal women to prevent osteoporosis. 相似文献