Kinase-negative mutants of S49 mouse lymphoma cells carry a trans-dominant mutation affecting expression of cAMP-dependent protein kinase.
Kinase-negative mutants of S49 mouse lymphoma cells are pleiotropically negative for all known cAMP-mediated responses of S49 cells and yield cell extracts which are deficient in cAMP binding activity and devoid of cAMP-dependent protein kinase activity. In hybrids between kinase-negative and wild-type cells, the mutant phenotype is dominant: the tetraploid hybrids have reduced cAMP-binding activity and undetectable cAMP-dependent kinase activity. The mutant phenotype is attributable to neither a soluble inhibitor of kinase catalytic subunit, nor a defective kinase regulatory subunit acting as an inhibitor, nor a defective catalytic subunit which sequesters regulatory subunits in inactive complexes. We propose that these mutants carry trans-dominant lesions in a regulatory locus responsible for setting intracellular levels of kinase expression.
D000242:Cyclic AMP / Q000378:metabolism; D005799:Genes, Dominant; D005809:Genes, Regulator; D006822:Hybrid Cells / Q000201:enzymology; D008223:Lymphoma / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D009374:Neoplasms, Experimental / Q000201:enzymology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics*
D047428:Protein Kinase Inhibitors; D000242:Cyclic AMP; D011494:Protein Kinases