Revertants of a trans-dominant S49 mouse lymphoma mutant that affects expression of cAMP-dependent protein kinase

Theodoor van Daalen Wetters, Michael P. Murtaugh, Philip Coffino

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Phenotypic revertants were isolated from an S49 mouse lymphoma tissue culture cell mutant that lacks cAMP-dependent protein kinase (cA-PK) activity (kin-). The mutant phenotype is trans-dominant and results from a lesion that probably lies outside the cA-PK subunit structural genes. The nature of the event that produces the kin- phenotype is unknown. However, the mechanism that is responsible for its behavior is genetically encoded because: spontaneous revertants arise at low frequency; reversion frequency is increased by mutagen treatment; mutagen-specific classes of revertant phenotypes are induced; and some revertants are temperature-sensitive for expression of cA-PK subunit polypeptides. Additional evidence is provided that argues against structural lesions in cA-PK catalytic (C) subunits as explanatory of the kin- phenotype. Kin- cells do not express an immunologically detectable C polypeptide, whereas C expression is restored in revertant cells. Revertants in which phenotype and cA-PK activity levels are only partially restored to that of wild-type cells contain a commensurately reduced amount of C polypeptide. Finally, the structure of C polypeptide in partial revertants is unaltered from that of wild-type C. The evidence supports the hypothesis that the kin- lesion defines a regulatory gene responsible for setting intracellular levels of cA-PK C subunit expression.

Original languageEnglish (US)
Pages (from-to)311-320
Number of pages10
Issue number1
StatePublished - Nov 1983

Bibliographical note

Funding Information:
We thank Dr. E. H. Fischer for providing us with purified bovine CA-PK catalytic subunit protein . This work was supported by National Science Foundation grant PCM-7807382. T. v. D. W. was supported by Public Health Service training grant 2 T32 CA09270-06 and P. C. is the recipient of a Research Career Development Award from the National Institutes of Health. The activities of M. P. M. were supported by National Institutes of Health grant AM28163.


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