Abstract
There are two major mechanisms of a general nature by which macro-molecules can gain entrance into intact, living cells (Pastan and Willingham, 1981a). One of these is generally referred to as fluid-phase endocytosis, which is a nonconcentrative, nonadsorptive mechanism that internalizes anything that happens to be in the surrounding medium of the cell. There are two basic organelles and pathways generally recognized for this process. In one of these, very small invaginations of the cell membrane at the surface pinch off and internalize as very small endocytic vesicles. These vesicles go directly to lysosomes, generally reaching them within minutes, where they fuse and dislodge their contents into these lysosomes. The other general process involves the fusing of large ruffles of the cell membrane, thus trapping into very large vesicles quite substantial quantities of the exterior medium. These large vacuoles or vesicles again travel rapidly to the area of lysosomal structures, and on impact these apper to shatter into many small vesicles, which subsequently fuse with the lysosomes.
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References
Brown, M. S., Anderson, R. G. W., and Goldstein, J. L., 1983, Recycling receptors: The round-trip itinerary of migrant membrane proteins, Cell 32: 663–667.
Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y., 1982, Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor- promoting phorbol esters, J. Biol. Chem. 257: 7847–7851.
Cohen, S., Carpenter, G., and King, L., 1980, Epidermal growth factor-receptor-protein kinase interactions, J. Biol. Chem. 255: 4834–4842.
Cooper, J.A., Bowen-Pope, D. F., Raines, E., Ross, R., and Hunter, T., 1982, Similar effects of platelet-derived growth factor on the phosphorylation of tyrosine in cellular protein, Cell 31: 263–273.
Cuatrecasas, P., 1982, Epidermal growth factor: Uptake and fate, Ciba Found. Symp. 92: 96–108.
Cuatrecasas, P., 1983a, Emerging concepts in the mechanism of action of membrane receptors, in: Affinity Chromatography and Biological Recognition ( I. M. Chaiken, M. Wilchek, and I. Parikh, eds.), Academic Press, Orlando, pp. 29–42.
Cuatrecasas, P., 1983b, Developing concepts in receptor research, Drug Intell. Clin Pharm. 17: 357–366.
Cuatrecasas, P., 1985, Emerging methods and concepts in the action of membrane receptors, in: Proceedings of the 1st International Conference New Methods in Drug Research, Vol 1 (A. Makriyannis, ed.) J. R. Prous Science, Barcelona, Spain, pp. 103–111.
Cuatrecasas, P., and Roth, T., (eds.), 1983, Receptor-MediatedEndocytosis, Receptors and Recognition Series, Chapman and Hall, London.
Dautry-Varsat, A., Ciechanover, A., and Lodish, H., 1983, pH and the recycling of transferrin during receptor-mediated endocytosis, Proc. Natl. Acad. Sci. U.S.A. 80: 2258–2262.
Denton, R. M., Brownsey, R. W., and Belsham, G. J., 1981, A partial view of the mechanism of insulin action, Diabetologia 21: 347–362.
Fox, C. F., and Das, M., 1979, Internalization and processing of the EGF receptor in the induction of DNA synthesis in cultured fibroblasts: The endocytic activation hypothesis, J. Supramol. Struct. 10: 199–214.
Grunberger, G., and Gorden, P., 1982, Affinity alteration of insulin receptor induced by a phorbol ester, Am. J. Physiol. 243: E319–E324.
Herzog, V., 1981, Pathways of endocytosis in secretory cells, Trends Biochem Sci. 1981: 319–322.
Jacobs, S., and Cuatrecasas, P., 1983, Insulin receptors, Annu. Rev. Pharmacol. Toxicol. 23: 461–479.
Jacobs, S., Sahyoun, N. E., Saltiel, A. R., and Cuatrecasas, P., 1983, Phorbol esters stimulate the phosphorylation of receptors for insulin and somatomedin C, Proc. Natl. Acad. Sci. U.S.A. 80: 6211–6213.
Kaibuchi, K., Takai, Y., Sawamura, M., Hoshijima, M., Fujikura, T., and Nishizuka, Y., 1983, Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation, J. Biol. Chem. 258: 6701–6704.
Karin, M., and Mintz, B., 1981, Receptor-mediated endocytosis of transferrin in develop- mentally totiputent mouse teratocarcinoma stem cells, J. Biol. Chem. 256: 3245–3252.
Kawahara, Y., Takai, Y., Minakuchi, R., Sano, K., and Nishizuka, Y., 1980, Phospholipid turnover as a possible transmembrane signal for protein phosphorylation during human platelet activation by thrombin, Biochem. Biophys. Res. Commun. 97: 309–317.
King, A. C., and Cuatrecasas, P., 1981, Peptide hormone-induced receptor mobility, aggregation, and internalization, N. Engl. J. Med. 305: 77–88.
King, A. C., and Cuatrecasas, P., 1982, Exposure of cells to an acidic environment reverses the inhibition by methylamine of the mitogenic response to epidermal growth factor, Biochem. Biophys. Res. Commun. 106: 479–485.
Klausner, R. D., Renswoude, J. V., Ashwell, G., Kempf, C. Schechter, A., Dean, A., and Bridges, R., 1983, Receptor-mediated endocytosis of transferrin in K562 cells, J. Biol. Chem. 58: 4715–4724.
Kolata, G., 1982, Is tyrosine the key to growth control, Science 219: 377–378.
Kull, F. C., Jr., Jacobs, S., Su, Y.-F., Svoboda, M. E., Van Wyk, J. J., and Cuatrecasas, P., 1983, Monoclonal antibodies to receptors for insulin and somatomedin-C, J. Biol. Chem. 258: 6561–6566.
Lapetina, E.G., and Siegel, F. L., 1983, Shape change induced in human platelets by platelet- activating factor, J. Biol. Chem. 258: 7241–7244.
Lapetina, E. G., and Siess, W., 1983, The role of phospholipase C in platelet responses, Life Sci. 33: 1011–1018.
May, W. S., Jacobs, S., and Cuatrecasas, P., 1984, The association of phorbol ester induced hyperphosphorylation and reversible regulation of transferrin membrane receptors in HL60 cells, Proc. Natl. Acad. Sci. U.S.A. 81: 2016–2020.
Niedle, J. E., Kuhn, L. J., and Vandenbark, G. R., 1983, Phorbol diester receptor copurifies with protein kinase C, Proc. Natl. Acad. Sci. U.S.A. 80: 36–40.
Pastan, I. H., and Willingham, M. C., 1981a, Receptor-mediated endocytosis of hormones in cultured cells, Annu. Rev. Physiol. 43: 239–250.
Pastan, I. H., and Willingham, M. C., 1981b, Journey to the center of the cell: Role of the receptosome, Science 214: 504–509.
Rosen, O. M., Herrera, R., Olowe, Y., Petruzzelli, L. M., and Cobb, M. H., 1983, Phos-phorylation activates the insulin receptor tyrosine protein kinase, Proc. Natl. Acad. Sci. U.S.A. 80: 3237–3240.
Rovera, G., Ferreo, D., Pagliardi, G. L., Vartikar, J., Pessano, S., Bottero, L., Abraham, S., and Lebman, D., 1982, Induction of differentiation of human myeloid leukemias by phorbol diesters: Phenotypic changes and mode of action, Ann. N.Y. Acad. Sci. 397: 211–220.
Sandvig, K., and Olsnes, S., 1981, Rapid entry of nicked diphtheria toxin into cells at low pH: Characterization of the entry process and effects of low pH on the toxin molecule, J. Biol. Chem. 256: 9068–9076.
Schiff, J. M., Fisher, M. M., and Underdown, B. J., 1984, Receptor-mediated biliary trans¬port of immunoglobulin A and asialoglycoprotein: Sorting and missorting of ligands revealed by two radiolabeling methods, J. Cell Biol. 98: 79–89.
Schlegal, R., Dickson, R. B., Willingham, M. C., and Pastan, I. H., 1982, Amantadine and dansylcadaverine inhibit vesicular stomatitis virus uptake and receptor-mediated endocytosis of a2-macroglobulin, Proc. Natl. Acad. Sci. U.S.A. 79: 2291–2295.
Sefton, B. M., Hunter, T., Beemon, K., and Eckhart, W., 1980, Evidence that the phos-phorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus, Cell 20: 807–816.
Sharkey, N. A., Leach, K. L., and Blumberg, P. M., 1984, Competitive inhibition by diacylglycerol of specific phorbol ester binding, Proc. Natl. Acad. Sci. U.S.A. 81: 607–610.
Shechter, Y., Chang, K.-J., Jacobs, S., and Cuatrecasas, P., 1979a, Modulation of binding and bioactivity of insulin by anti-insulin antibody: Relation to possible role of receptor self-aggregation in hormone action, Proc. Natl. Acad. Sci. U.S.A. 76: 2720–2724.
Shechter, Y., Hernaez, L., Schlessinger, J., and Cuatrecasas, P., 1979b, Local aggregation of hormone-receptor complexes is required for activation by epidermal growth factor, Nature 278: 835–838.
Shoyab, M., DeLarco, J. E., and Todaro, G. J., 1979, Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors, Nature 279: 387–391.
Siess, W., Siegel, F. L., and Lapetina, E. G., 1983, Arachidonic acid stimulates the formation of 1,2-diacylglycerol and phosphatidic acid in human platelets, J. Biol. Chem. 258: 11236–11242.
Takai, Y., Kaibuchi, K., Matsubara, T., and Nishizuka, Y., 1981, Inhibitory action of guan- osine 3’,5’-monophosphate on thrombin-induced phosphatidylinositol turnover and protein phosphorylation in human platelets, Biochem. Biophys. Res. Commun. 101: 61–67.
Thomopoulos, P., Testa, Y., Gourdin, M., Hervy, C., Titeur, M., and Vainchenker, W., 1982, Inhibition of insulin receptor binding by phorbol esters, Eur. J. Biochem. 129: 389–393.
Willingham, M. C., Hanover, J. A., Dickson, R. B., and Pastan, I., 1984, Morphologic characterization of the pathway of transferrin endocytosis and recycling in human KB cells, Proc. Natl. Acad. Sci. U.S.A. 81: 175–179.
Zick, Y., Kasuga, M., Kahn, C. R., and Roth, J., 1983a, Characterization of insulin-mediated phosphorylation of the insulin receptor in a cell-free system, J. Biol. Chem. 258: 75–80.
Zick, Y., Whittaker, J., and Roth, J., 1983b, Insulin stimulated phosphorylation of its own receptor, J. Biol. Chem, 258: 3431–3434.
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© 1985 Plenum Press, New York
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Cuatrecasas, P. (1985). Internalization and Processing of Peptide Hormone Receptors. In: Poste, G., Crooke, S.T. (eds) Mechanisms of Receptor Regulation. New Horizons in Therapeutics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2131-6_13
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DOI: https://doi.org/10.1007/978-1-4613-2131-6_13
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