Kinase-negative mutants of S49 mouse lymphoma cells carry a trans-dominant mutation affecting expression of

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R A Steinberg, T van Daalen Wetters, P Coffino

    Cell
    |December 1, 1978
    PubMed

    Insights

    Kinase-negative mutants of S49 cells lack cyclic adenosine monophosphate (cAMP) responses and kinase activity. These mutant traits are dominant, suggesting a trans-dominant lesion affecting kinase expression regulation.

    Area of Science:

    • Cellular biology
    • Biochemistry
    • Genetics

    Background:

    • S49 mouse lymphoma cells are a model for studying cyclic adenosine monophosphate (cAMP) signaling.
    • cAMP-dependent protein kinase (PKA) is crucial for mediating cellular responses to cAMP.
    • Kinase-negative mutants exhibit a complete loss of all known cAMP-mediated responses.

    Purpose of the Study:

    • To investigate the molecular basis of kinase-negative mutants in S49 cells.
    • To determine the mechanism underlying the dominant inheritance of the mutant phenotype in hybrid cells.
    • To identify the genetic locus responsible for regulating cAMP-dependent protein kinase expression.

    Main Methods:

    • Analysis of cAMP binding activity in cell extracts.
    • Assay of cAMP-dependent protein kinase activity.
    • Creation and characterization of somatic cell hybrids between mutant and wild-type cells.

    Main Results:

    • Kinase-negative mutants show deficient cAMP binding and absent PKA activity.
    • The kinase-negative phenotype is dominant in tetraploid hybrids, with reduced cAMP binding and undetectable PKA activity.
    • The mutant phenotype is not caused by soluble inhibitors, defective regulatory subunits, or sequestration of catalytic subunits.

    Conclusions:

    • The kinase-negative phenotype is attributed to a trans-dominant lesion.
    • This lesion resides in a regulatory locus controlling intracellular PKA expression levels.
    • Further studies are needed to pinpoint the specific genetic defect.

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