Regulation of tyrosinase in human melanocytes grown in culture

Tyrosinase, the enzyme that controls the synthesis of melanin, is a unique product of melanocytes. Normal and malignant human melanocytes grown in culture were used to study the factors that regulate the expression of tyrosinase. Immunoprecipitation experiments showed that newly synthesized tyrosinase appeared as a protein with an apparent molecular weight of 70,000 that was processed to a protein with an apparent molecular weight of 80,000. Neither tunicamycin nor 2-deoxy-D- glucose inhibited this conversion, suggesting that O-glycosylation is the major biochemical event in the posttranslational modification of tyrosinase. Agents that stimulated the proliferation of normal melanocytes also stimulated tyrosinase activity. Melanocytes with low levels of tyrosinase activity synthesized less tyrosinase, processed the enzyme more slowly, and degraded it more rapidly than melanocytes with high levels of tyrosinase activity. We conclude that tyrosinase activity in cultures of human melanocytes derived from different donors is determined predominantly by its abundance.

[1]  J. Cairncross,et al.  Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets , 1982, The Journal of experimental medicine.

[2]  J. Elting,et al.  Temporal aspects of the N- and O-glycosylation of human chorionic gonadotropin. , 1982, The Journal of biological chemistry.

[3]  M. Eisinger,et al.  Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[4]  V. Hearing,et al.  Mammalian tyrosinase: isozymic forms of the enzyme. , 1981, The International journal of biochemistry.

[5]  U. Francke,et al.  Supermelanotic hybrids derived from mouse melanomas and normal mouse cells , 1980, Somatic cell genetics.

[6]  R. Schwarz,et al.  Interference with glycosylation of glycoproteins. Inhibition of formation of lipid-linked oligosaccharides in vivo. , 1979, The Biochemical journal.

[7]  W. Mahoney,et al.  Biological activities of the two major components of tunicamycin. , 1979, The Journal of biological chemistry.

[8]  E. Huberman,et al.  Stimulation of differentiated functions in human melanoma cells by tumor-promoting agents and dimethyl sulfoxide. , 1979, Cancer research.

[9]  K. Nishioka.  Particulate Tyrosinase of Human Malignant Melanoma , 1978 .

[10]  V. Hearing,et al.  Mammalian tyrosinase. Structural and functional interraltionship of isozymes. , 1978, Biochimica et biophysica acta.

[11]  R. Halaban,et al.  Tyrosinase and inhibition of proliferation of melanoma cells and fibroblasts. , 1977, Experimental cell research.

[12]  R. Halaban,et al.  The dual effect of melanocyte-stimulating hormone (MSH) on the growth of cultured mouse melanoma cells. , 1977, Experimental cell research.

[13]  R. King,et al.  Hairbulb tyrosinase activity in oculocutaneous albinism , 1976, Nature.

[14]  P. Fritsch,et al.  Association of cell surface receptors for melanotropin with the Golgi region in mouse melanoma cells. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Halaban,et al.  Melanoma cells which require cyclic AMP for growth , 1975, Nature.

[16]  S W Kessler,et al.  Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. , 1975, Journal of immunology.

[17]  S. Pomerantz,et al.  Tyrosinase activity in human skin. Influence of race and age in newborns. , 1975, The Journal of clinical investigation.

[18]  J. Pawelek,et al.  Regulation of melanocyte stimulating hormone action at the receptor level: discontinuous binding of hormone to synchronized mouse melanoma cells during the cell cycle. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. Pomerantz,et al.  Purification and properties of tyrosinase isoenzymes from hamster melanoma. , 1973, The Yale journal of biology and medicine.

[20]  J. Pawelek,et al.  Molecular biology of pigment cells. Molecular controls in mammalian pigmentation. , 1973, The Yale journal of biology and medicine.

[21]  F. Melchers.  Biosynthesis, intracellular transport, and secretion of immunoglobulins. Effect of 2-deoxy-D-glucose in tumor plasma cells producing and secreting immunoglobulin G1. , 1973, Biochemistry.

[22]  J. Pawelek,et al.  Control of phenotypic expression of cultured melanoma cells by melanocyte stimulating hormones. , 1973, Nature: New biology.

[23]  N. Ohtaki,et al.  Antiserum against tyrosinase from mouse melanoma. , 1972, The Journal of investigative dermatology.

[24]  A. Takatsuki,et al.  Effect of tunicamycin on the synthesis of macromolecules in cultures of chick embryo fibroblasts infected with Newcastle disease virus. , 1971, The Journal of antibiotics.

[25]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[26]  W. C. Quevedo,et al.  Electrophoretic variations of tyrosinase in follilar melanocytes during the hair growth cycle in mice. , 1969, The Journal of experimental zoology.

[27]  S. Pomerantz.  L-Tyrosine-3, 5-3H Assay for Tyrosinase Development in Skin of Newborn Hamsters , 1969, Science.

[28]  H. Seiler,et al.  Separation and characterization of multiple forms of tyrosinase from mouse melanoma. , 1967, Cancer research.

[29]  A. Lerner,et al.  MELANOCYTE-STIMULATING HORMONE AND ADRENOCORTICOTROPHIC HORMONE. THEIR RELATION TO PIGMENTATION. , 1964, The New England journal of medicine.

[30]  A. Lerner,et al.  EFFECTS OF TRICOSAPEPTIDE “ACTH” AND ALPHA‐MELANOCYTE‐STIMULATING HORMONE ON THE SKIN COLOR OF MAN * , 1963 .