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Stable variants of the macrophage-like cell line J774.2, defective in adenylate cyclase and protein kinase activities, were selected by cloning cells resistant to the growth-inhibitory effect of cholera toxin and 8-bromo-adenosine 3':5' cyclic monophosphoric acid (8 Br-cAMP), respectively. These variants were analyzed for their ability to respond to cyclic AMP-mediated enhancement of phagocytosis and cyclic AMP-mediated inhibition of plasminogen activator secretion and growtn. The adenylate cyclase variants were unaffected by cholera toxin but were sensitive to 8 Br-cAMP-mediated inhibition of plasminogen activator secretion and growth. One of these variants exhibited a defect in phagocytosis that could be corrected by 8 Br-cAMP. The protein kinase variants exhibited normal basal phagocytosis that could not be stimulated by either 8 Br-cAMP or cholera toxin; they were also insensitive to cyclic AMP-mediated inhibition of plasminogen activator secretion and growth. The studies demonstrate that the three effects of cyclic AMP in J774.2--inhibition of growth and plasminogen activator secretion, and enhancement of basal Fc-mediated phagocytosis--are mediated by a cyclic AMP-dependent portein kinase. The results support the usefulness of variants in cyclic nucleotide metabolism in understanding the regulation of differentiated cell function by cyclic AMP.
N Rosen, and
J Piscitello, and
J Schneck, and
R J Muschel, and
B R Bloom, and
O M Rosen
November 1984,
Journal of immunology (Baltimore, Md. : 1950),
N Rosen, and
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J Schneck, and
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B R Bloom, and
O M Rosen
February 1983,
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N Rosen, and
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O M Rosen
September 1988,
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N Rosen, and
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July 1985,
Biochimica et biophysica acta,
N Rosen, and
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November 1989,
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N Rosen, and
J Piscitello, and
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January 1983,
Proceedings of the National Academy of Sciences of the United States of America,
N Rosen, and
J Piscitello, and
J Schneck, and
R J Muschel, and
B R Bloom, and
O M Rosen
November 1984,
Journal of immunology (Baltimore, Md. : 1950),
N Rosen, and
J Piscitello, and
J Schneck, and
R J Muschel, and
B R Bloom, and
O M Rosen
March 1984,
Biochimica et biophysica acta,
N Rosen, and
J Piscitello, and
J Schneck, and
R J Muschel, and
B R Bloom, and
O M Rosen
April 1982,
Proceedings of the National Academy of Sciences of the United States of America,
N Rosen, and
J Piscitello, and
J Schneck, and
R J Muschel, and
B R Bloom, and
O M Rosen
February 1993,
The Journal of general physiology,
