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101.
Low density lipoprotein receptor-related protein mediates endocytosis of monoclonal antibodies in cultured cells and rabbit liver 总被引:10,自引:0,他引:10
J Herz R C Kowal Y K Ho M S Brown J L Goldstein 《The Journal of biological chemistry》1990,265(34):21355-21362
Monoclonal antibodies that bound to the external domain of the rabbit low density lipoprotein receptor-related protein (LRP) were taken into rabbit fibroblasts by receptor-mediated endocytosis. Uptake occurred in fibroblasts from Watanabe-heritable hyperlipidemic rabbits, which lack low density lipoprotein receptors, as well as in normal rabbit fibroblasts. The fate of the internalized antibodies differed, depending on the domain of LRP that was recognized. LRP is synthesized as a single polypeptide chain that is cleaved to form a heterodimer of two noncovalently bound proteins, 1) a 515-kDa subunit that contains the binding domain, and 2) an 85-kDa subunit that contains the membrane-spanning region and cytoplasmic tail. A monoclonal antibody directed against the 515-kDa subunit (anti-LRP 515) rapidly dissociated from LRP at pH 5.2. After uptake by cells this antibody dissociated from the receptor and was degraded in lysosomes. A second antibody directed against the external portion of the 85-kDa subunit (anti-LRP 85) failed to dissociate at acid pH. After uptake by cells this antibody was not degraded, but instead was released from the cells in an acid-precipitable form. When administered intravenously to rabbits, both 125I-labeled antibodies were rapidly cleared from the circulation, 75-95% of the uptake occurring in the liver. The anti-LRP 515 antibody was degraded and acid-soluble products appeared in the plasma. No significant acid-soluble products appeared when the anti-LRP-85 antibody was infused. We conclude that LRP can carry out receptor-mediated endocytosis and that its ligand-binding domain, like the similar domain of the low density lipoprotein receptor, undergoes an acid-dependent conformational change that ejects ligands within the endosome. We also conclude that in the body this endocytotic function is expressed primarily in the liver. Both of these conclusions lend support to the hypothesis that LRP may function in humans and animals as a receptor for apolipoprotein E-enriched lipoproteins, such as chylomicron remnants. 相似文献
102.
K H Weisgraber R W Mahley R C Kowal J Herz J L Goldstein M S Brown 《The Journal of biological chemistry》1990,265(36):22453-22459
The binding of native rabbit beta-very low density lipoproteins (beta-VLDL) to the low density lipoprotein receptor-related protein (LRP) requires incubation with exogenous apolipoprotein (apo) E. Inclusion of a mixture of the C apolipoproteins in the incubation inhibits this binding. In the present study, the ability of the individual C apolipoproteins (C-I, C-II, and C-III) to block binding of beta-VLDL to the LRP was examined by measuring cholesteryl ester formation in mutant fibroblasts that lack low density lipoprotein receptors or by measuring binding to the LRP using ligand blotting. In each assay, both apoC-I and apoC-II inhibited binding; apoC-I was the more effective inhibitor. Apolipoprotein C-III had no effect on binding activity, regardless of its sialylation level. Binding of human apoE to rabbit beta-VLDL in the absence or presence of human apoC-I, apoC-II, and monosialo-apoC-III was also determined, by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results of these studies are consistent with a mechanism in which exogenous human apoE displaces the endogenous apoE and the beta-VLDL particle becomes enriched with apoE (by 4.2-fold in this study). At this higher apoE content, the beta-VLDL bound to the LRP. Inclusion of apoC-I, apoC-II, or apoC-III in the incubation mixture resulted in a differential displacement of apoE from the beta-VLDL; however, at the concentrations examined, only apoC-I and apoC-II were capable of displacing sufficient apoE to abolish binding to LRP. 相似文献
103.
104.
Fritz Herz Alexander Schermer Murray Halwer Lee H. Bogart 《Archives of biochemistry and biophysics》1981,212(2):581-588
HT-29, a cell line derived from a human colon carcinoma, exhibits very low alkaline phosphatase activity. The enzyme is thermolabile and is of the intestinal type. Hyperosmolality and/or sodium butyrate induce increased levels of activity. The increase is most pronounced with HT-29 cells growing in hyperosmolar medium containing sodium butyrate. Under these conditions specific activity rises over 1000-fold. The effect of hyperosmolality is blocked by cycloheximide and that of sodium butyrate by thymidine, cordycepin, and cycloheximide. By contrast to other human cancer cell lines, the enzyme of HT-29 is not influenced by cell density and glucocorticoid hormones. 5-Bromo-2′-deoxyuridine and inhibitors of DNA synthesis cause a slight increase in specific activity. 相似文献
105.
Thermal Denaturation of Native Striatal Tyrosine Hydroxylase: Increased Thermolability of the Phosphorylated Form of the Enzyme 总被引:5,自引:5,他引:0
Mitchell A. Lazar Roger J. W. Truscott Joachim D. Raese Jack D. Barchas 《Journal of neurochemistry》1981,36(2):677-682
Tyrosine hydroxylase was purified from bovine corpus striatum. The native enzyme had a half-life of 15 +/- 3 min at 50 degrees C. Phosphorylation of tyrosine hydroxylase with protein kinase purified from both corpus striatum and heart activated the enzyme, but activity was rapidly lost with additional preincubation of the enzyme at 30 degrees C. Thermal denaturation studies indicated that phosphorylated tyrosine hydroxylase had a half-life of 5 +/- 2 min at 50 degrees C 相似文献
106.
107.
108.
The genetic variability of membrane proteins (structure-bound proteins) and cytosol proteins (water-soluble proteins) was investigated in two inbred strains of the mouse, C57BL/6J and DBA/2J. Membrane proteins and cytosol were isolated from the brain and liver of the mouse. The proteins were separated by two-dimensional electrophoresis. A high number of genetic variant proteins (brain, 30; liver, 72) was found in the cytosol. Most of these variants represented changes in the amount of proteins. Electrophoretic mobility changes occurred only in about 1% (brain, 6; liver, 9) of all protein spots of a two-dimensional pattern. In contrast to the cytosol proteins, no genetic variation was detected among the membrane proteins, not even for the quantitative characteristics of the protein spots. The results obtained for the two classes of proteins suggest that the degree of variability in the amount of proteins is related to the degree of variability in the structure of proteins. 相似文献
109.
A facile chemical synthesis of 1,2-dioleoyl and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine as well as the synthesis of several deuterated derivatives of phosphatidylserine (2 and 3 positions of serine and in the 3-glycerol position) are described. 360 MHz 1H NMR spectra of phosphatidylserine and the optical activity of various phosphatidylserine diastereomers were measured. 相似文献
110.
l-(+)-Bornesitol was detected in 23 of 33 genera of Gentianaceae investigated. The only subtribe without l-(+)-bornesitol (3 species tested) was Exacinae. None of the five genera of Menyanthaceae examined were found to contain l-(+)-bornesitol. 相似文献