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41.
Peptide analogues compete with the binding of alpha-factor to its receptor in Saccharomyces cerevisiae 总被引:2,自引:0,他引:2
alpha-Factor, a secreted tridecapeptide pheromone, is required for mating between the a- and alpha-haploid mating types of Saccharomyces cerevisiae. An analogue of alpha-factor, [DHP8,DHP11,Nle12] tridecapeptide (where DHP represents 3,4-dehydro-L-proline and Nle represents norleucine), was catalytically reduced in the presence of 3H gas to produce a radiolabeled pheromone with high specific activity, purity, and biological activity. Association and dissociation kinetics indicated values of 4.9 x 10(4) M-1 s-1 for k1 and 1.1 x 10(-3) s-1 for k-1. Saturation binding studies gave an equilibrium dissociation constant equal to 2.3 x 10(-8) M, which approximated the kinetically derived KD of 2.2 x 10(-8) M. These values compare favorably to the previously determined KD of 6 x 10(-9) M (Jenness, D.D., Burkholder, A.C., and Hartwell, L.H. (1986) Mol. Cell. Biol. 6, 318-320). Scatchard analysis and dissociation in the presence of excess unlabeled ligand indicated interaction with a homogeneous population of noninteracting binding sites (13,000 sites/cell). A number of alpha-factor analogues, previously investigated for their structure-function relationships (Naider, F., and Becker, J.M. (1986) CRC Crit. Rev. Biochem. 21, 225-249), were used to compete with [3H]alpha-factor binding. Four tridecapeptides having conservative amino acid replacements bound strongly to the receptor. In contrast, [Phe3]alpha-factor and 10 des-Trp1-alpha-factor analogues bound to the receptor 1-3 orders of magnitude less effectively than did alpha-factor itself. The binding constants for all active pheromones correlated with biological activity. However, des-Trp1[Phe3]alpha-factor and des-Trp1-[Ala3]alpha-factor, which were not biologically active, still competed with alpha-factor binding, indicating that these analogues fail to induce a secondary signal necessary for biological response to the pheromone. One analogue, des-Trp1-[Cha3,L-Ala9]alpha-factor (where Cha represents cyclohexylalanine), was not biologically active and did not demonstrate binding to the receptor, whereas des-Trp1-[Cha3,D-Ala9]alpha-factor was active and bound to the receptor. This finding suggests that a type II beta-turn is necessary for binding of alpha-factor to its receptor and for subsequent biological activity. 相似文献
42.
Leukocyte stimulation: receptor, membrane, and metabolic events. Introduction and summary 总被引:5,自引:0,他引:5
E L Becker 《Federation proceedings》1986,45(7):2148-2150
43.
Hepatic arterial infusion chemotherapy (HAIC) for unresectable hepatic neoplasms has been associated with gastric ulcers and epithelial atypia that may be misinterpreted as carcinoma. Gastric brushings were reviewed from six patients who developed gastric ulcers with histologically proven atypia following HAIC. Marked cytologic atypia, reminiscent of a pronounced radiation effect, was present in gastric epithelial cells in five patients. The atypical cells occurred singly or in small sheets. They were markedly enlarged but a low nuclear-cytoplasmic ratio was preserved. The abundant cytoplasm was vacuolated or foamy. Binucleation and multinucleation were common, and massive nucleoli were characteristic. The brushings also contained the reparative, inflammatory and necrotic changes associated with usual benign gastric ulcers. The bizarre atypia associated with HAIC can be a source of misdiagnosis of cancer in cytologic as well as in histologic specimens. 相似文献
44.
Is a rise in intracellular concentration of free calcium necessary or sufficient for stimulated cytoskeletal-associated actin? 总被引:14,自引:10,他引:4 下载免费PDF全文
R I Sha'afi J Shefcyk R Yassin T F Molski M Volpi P H Naccache J R White M B Feinstein E L Becker 《The Journal of cell biology》1986,102(4):1459-1463
The addition of the calcium ionophore A23187 to rabbit neutrophils increases the amount of actin associated with the cytoskeleton regardless of the presence or absence of calcium in the incubation medium. In the presence of extracellular calcium, the effect of A23187 is biphasic with respect to concentration. The action of the ionophore is rapid, transient, and is inhibited by pertussis toxin, hyperosmolarity, and quinacrine. On the other hand, the addition of pertussis toxin or hyperosmolarity has small if any, effect on the rise in intracellular calcium produced by A23187. While quinacrine does not affect the fMet-Leu-Phe-induced increase in cytoskeletal actin and the polyphosphoinositide turnover, its addition inhibits completely the stimulated increase in Ca-influx produced by the same stimulus. The results presented here suggest that a rise in the intracellular concentration of free calcium is neither necessary nor sufficient for the stimulated increase in cytoskeletal-associated actin. A possible relationship between the lipid remodeling stimulated by chemoattractants and the increased cytoskeletal actin is discussed. 相似文献
45.
46.
Analogues of the des-1-tryptophan,3-beta-cyclohexylalanine-alpha-factor of Saccharomyces cerevisiae, where the glycyl residue of position 9 was replaced by D-Ala, L-Ala, D-Leu, and L-Leu, were synthesized and evaluated by morphogenesis assays and circular dichroism spectroscopy. Synthesis was accomplished in solution phase with mixed anhydrides and p-nitrophenyl active esters as the coupling agents. All crude dodecapeptides were purified to greater than 98% homogeneity by preparative high-performance liquid chromatography on a reversed-phase column. The Gly9, D-Ala9, and D-Leu9 analogues elicited morphogenic alterations in MATa strains of S. cerevisiae at concentrations of 1-2 micrograms/mL and exhibited similar CD patterns in both trifluoroethanol and tris(hydroxymethyl)aminomethane buffer, pH 7.4. In contrast, the L-Ala9 and L-Leu9 analogues were more than 200 times less active in the morphogenesis assay and had markedly different CD spectra. These results demonstrate that the position 9 residue plays an important role in determining the biological activity and solution conformation of alpha-factor. We suggest the presence of a type II beta-turn in the Lys7-Gln10 region when the alpha-factor assumes its biologically active conformation. 相似文献
47.
The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin 总被引:21,自引:2,他引:19 下载免费PDF全文
E L Becker J C Kermode P H Naccache R Yassin M L Marsh J J Munoz R I Sha'afi 《The Journal of cell biology》1985,100(5):1641-1646
Pertussis toxin treatment of rabbit peritoneal neutrophils causes a concentration-dependent inhibition of granule enzyme secretion induced by formylmethionyl-leucyl-phenylalanine, C5a, and leukotriene B4. It also inhibits chemotaxis induced by formylmethionyl-leucyl-phenylalanine. The same toxin treatment, however, has no effect on granule enzyme secretion induced by the calcium ionophore A23187 or phorbol 12-myristate 13-acetate. Moreover, pertussis toxin treatment does not affect either the number or affinity of the formylpeptide receptors on the neutrophil nor does it have any effect on the unstimulated levels of cyclic AMP (cAMP) or the transient rise in cAMP induced by chemotactic factor stimulation in these cells. We hypothesize that pertussis toxin, as in other cells, interacts with a GTP binding regulatory protein identical with or analogous to either Ni or transducin which mediates the receptor-induced inhibition or activation of a target protein or proteins required in neutrophil activation. The nature of the target protein is unknown, but it is not the catalytic unit of adenylate cyclase. The target protein acts after binding of chemotactic factor to its receptor in the sequence that leads to the receptor-induced rise in intracellular Ca2+. It does not affect the responses elicited by the direct introduction of calcium into the cells or the activity of protein kinase C. 相似文献
48.
Pseudomonas aeruginosa strain PAO1 was compared to PAO1 strains containing an IncP-1 R plasmid (RP1, R68, or R68.45) in an experimental mouse burn infection model. All R plasmids tested caused a 10- to 400-fold increase in mean lethal dose (LD50). The decrease in virulence produced by plasmids R68 and R68.45 was significantly greater than the decrease caused by the closely related plasmid RP1. All plasmids also led to an increased sensitivity of strain PAO1 to human serum bactericidal activity. Virulence and serum resistance of strain PAO1 were restored by curing of the entire plasmid R68.45 but not by deletions in the plasmid's transfer gene regions. 相似文献
49.
Sensitization to stress: the enduring effects of prior stress on amphetamine-induced rotational behavior 总被引:2,自引:0,他引:2
In rats with a unilateral 6-OHDA lesion of the substantia nigra exposure to footshock or immobilization stress produced a long-lasting enhancement in the rotational behavior evoked by a subsequent injection of amphetamine. However, the effect was dependent on the environmental context in which stress was applied. It is suggested that stress may induce enduring changes in brain and behavior similar to those produced by psychomotor stimulant drugs. 相似文献
50.
Clifford A. L. Becker 《Inorganica chimica acta》1985,100(2):227-233
Equilibrium constants, Kdis, for the solvent- dependent, solution-phase disproportionation equilibria of monosubstituted pentakis(arlisocyanide)cobalt(I) complexes: 2[Co(CNR)4L]+?[Co(CNR)3L2]+ + [Co(CNR)5]+, Kdis = are measured by planimeter-integration of proton- NMR spectra at ambient temperature. The complexes, [Co(CNR)4L]ClO4, R = 2,6-Me2C6H3, L = P(C6H5)3, P(C6H4Cl-p)3, P(OC6H5)3, P(OC6H4Cl-p)3; R = o-MeC6H4, L = P(C6H4Cl-p)3, P(OC6H5)3, P(OC6H4Cl-p)3; R = 2,4,6-Me3C6H2, L = P(C6H5)3; R = 2,6-Et2C6H3, L = P(C6H5)3; are investigated in the deuterated solvents, CDCl3, CD3CN, (CD3)2CO, C5D5N, CD3NO2, and (CD3)2SO. Disproportionation seems to occur in all [Co(CNR)4L]+, but NMR study is facilitated by utilizing equivalent alkyl protons (i.e., Me-groups) on the RNC ligands.Correlation of Kdis values with steric-hindrance of the RNC in sets of complexes with the same P-ligand is evident in all solvents: Kdis decreases with increased steric-hindrance in RNC. The Kdis values for complexes with the same RNC and analogous triarylphosphine, triarylphosphite ligands (i.e., PR3, P(OR)3, same R) are approximately equal. The Kdis values for complexes of P-ligands with Cl-substituent are significantly larger than Kdis values for complexes with the corresponding unsubstituted P-ligands (e.g., [Co(CNR)4P(C6H4Clp)3]ClO4vs. [Co(CNR)4P(C6H5)3]ClO4) in (CD3)2CO and C5D5N solution, but are smaller in CDCl3 and CD3CN, and approximately equal in CD3NO2 and (CD3)2SO. Properties of the solvents are also considered. 相似文献