Enhancement of protein kinase C-mediated EGF receptor phosphorylation by auranofin.

The lipophilic anti-inflammatory and immunoregulatory gold (I) complex, 2,3,4,6-tetra-O-acetyl-l-thio-β-D-glucopyranosato-S-[triethylphosphine] gold (auranofin) is now widely used in the treatment of rheumatoid arthritis (1). Although the specific biochemical action(s) of auranofin are not known, the drug has been shown to react readily with thiol groups (2). Such interactions may alter the activity of key enzymes either by direct involvement with the catalytic site or through allosteric effects. Several reports have indicated that auranofin can modulate cellular activation responses which involve the Ca2+-activated, phospholipid-dependent protein kinase (PKC). For example, low concentrations of auranofin (< 1 μM) enhance–and higher concentrations inhibit–the production of superoxide in neutrophils incubated with phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA), a known activator of PKC (3).

[1]  M. Froscio,et al.  Auranofin enhances phosphorylation of putative substrates of protein kinase C in human platelets. , 1988, Biochemical pharmacology.

[2]  S. Crooke,et al.  Effect of auranofin and other gold complexes on the activity of phospholipase C. , 1987, Molecular pharmacology.

[3]  N. Hurst,et al.  Auranofin increases the affinity of phorbol dibutyrate receptors in chronic lymphocytic leukemia cells (B cells). , 1987, Journal of immunology.

[4]  M. Froscio,et al.  Inhibition of epidermal growth factor binding to HeLa cells by auranofin. , 1987, Biochemical pharmacology.

[5]  S. Crooke,et al.  The cellular and molecular pharmacology of auranofin and related gold complexes. , 1986, Scandinavian journal of rheumatology. Supplement.

[6]  A. Ullrich,et al.  The complete primary structure of protein kinase C--the major phorbol ester receptor. , 1986, Science.

[7]  G. Nuki,et al.  Studies of the effect of D-penicillamine and sodium aurothiomalate therapy on superoxide anion production by monocytes from patients with rheumatoid arthritis: evidence for in vivo stimulation of monocytes. , 1986, Annals of the rheumatic diseases.

[8]  J. Downward,et al.  Autophosphorylation and protein kinase C phosphorylation of the epidermal growth factor receptor. Effect on tyrosine kinase activity and ligand binding affinity. , 1985, The Journal of biological chemistry.

[9]  R. Davis,et al.  Tumor-promoting phorbol diesters cause the phosphorylation of epidermal growth factor receptors in normal human fibroblasts at threonine-654. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Davis,et al.  sn-1,2-Dioctanoylglycerol. A cell-permeable diacylglycerol that mimics phorbol diester action on the epidermal growth factor receptor and mitogenesis. , 1985, The Journal of biological chemistry.

[11]  R. N. Brogden,et al.  Auranofin. A preliminary review of its pharmacological properties and therapeutic use in rheumatoid arthritis. , 1984, Drugs.

[12]  B. Seligmann,et al.  Auranofin affects early events in human polymorphonuclear neutrophil activation by receptor-mediated stimuli. , 1984, Journal of immunology.

[13]  M. Waterfield,et al.  Anti epidermal growth factor receptor monoclonal antibodies , 1983 .

[14]  P. Davis,et al.  A longitudinal study of in vitro tests for lymphocyte function in rheumatoid arthritis , 1978, Annals of the rheumatic diseases.

[15]  H. Herschman,et al.  Variants of 3T3 cells lacking mitogenic response to epidermal growth factor. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[16]  G. Todaro,et al.  Nerve growth factor receptors on human melanoma cells in culture. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[17]  S. Cohen,et al.  Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. , 1972, The Journal of biological chemistry.

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