Evidence suggesting that a cyclic AMP‐dependent protein kinase is a positive regulator of proliferation in Cloudman S91 melanoma cells

Wild‐type Cloudman S91 melanoma cells have a retarded rate of division when agents which raise cyclic AMP levels such as melanotropin, protaglandin E1, or cholera toxin are supplemented to the culture medium. A mutant cell line was isolated which had the opposite response, i.e., the mutant grew very slowly unless agents which raised cyclic AMP levels were present (Pawelek et al., '75a). In this report evidence is presented indicating that the molecular basis for the mutant phenotype resides in the major cyclic AMP‐dependent protein kinase found in the cells. The mutant kinase had increased thermolability and an elevated activation constant for cyclic AMP over the corresponding wild‐type kinase. It is proposed that the elevated requirement for cyclic AMP for the proliferation of cAdep cells is related to the elevated activation constant of this kinase, suggesting that the kinase is a positive regulator of proliferation in Cloudman S91 cells.

[1]  M. Raff,et al.  Cyclic AMP as a mitogenic signal for cultured rat Schwann cells , 1978, Nature.

[2]  C. Byus,et al.  Type I and type II cyclic AMP-dependent protein kinase as opposite effectors of lymphocyte mitogenesis , 1977, Nature.

[3]  J. Pawelek,et al.  Activation of melanoma tyrosinase by a cyclic AMP-dependent protein kinase in a cell-free system , 1977, Nature.

[4]  D. Friedman.  Role of cyclic nucleotides in cell growth and differentiation. , 1976, Physiological reviews.

[5]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[6]  G. Goldhaber,et al.  Adenosine 3': 5'-cyclic monophosphate as a possible mediator in the proliferative effect of prolactin on the pigeon crop sac. , 1976, The Journal of endocrinology.

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

[8]  H. Bourne,et al.  A structural gene mutation affecting the regulatory subunit of cyclic AMP-dependent protein kinase in mouse lymphoma cells. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H. Bourne,et al.  Cyclic AMP-dependent protein kinase: pivotal role in regulation of enzyme induction and growth , 1975, Science.

[10]  W. Rutter,et al.  Positive control of cyclic AMP on mesenchymal factor controlled DNA synthesis in embryonic pancreas , 1975, Nature.

[11]  H. Bourne,et al.  Mechanism of lymphoma cell death induced by cyclic AMP. , 1975, The American journal of pathology.

[12]  J. Pawelek,et al.  Melanocyte-stimulating hormone promotes activation of pre-existing tyrosinase molecules in Cloudman S91 melanoma cells , 1975, Nature.

[13]  W. Rudert,et al.  Cyclic adenosine 3':5'-monophosphate and the induction of deoxyribonucleic acid synthesis in liver. , 1975, The Journal of biological chemistry.

[14]  G. S. Johnson,et al.  Role of cyclic nucleotides in growth control. , 1975, Annual review of biochemistry.

[15]  A. Pardee,et al.  A restriction point for control of normal animal cell proliferation. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

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

[17]  G. P. Talwar,et al.  Role of cyclic AMP in mitogen induced transformation of human peripheral leukocytes. , 1973, Journal of immunology.

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

[19]  D. Boylan,et al.  Effect of Seawater Soluble Fraction of Kerosene on Chemotaxis in a Marine Snail, Nassarius obsoletus , 1973, Nature.

[20]  D. Franks,et al.  Increases in rat liver cyclic AMP concentrations prior to the initiation of DNA synthesis following partial hepatectomy or hormone infusion. , 1972, Biochemical and biophysical research communications.

[21]  J. Whitfield,et al.  Stimulation of DNA synthesis and mitotic activity of thymic lymphocytes by cyclic adenosine 3'5'-monophosphate. , 1969, Experimental cell research.

[22]  T. Puck,et al.  Genetics of somatic mammalian cells, VII. Induction and isolation of nutritional mutants in Chinese hamster cells. , 1968, Proceedings of the National Academy of Sciences of the United States of America.