Date of Award


Degree Type


Degree Name

Doctor of Philosophy


L6 myoblasts are a permanent rat skeletal myoblast cell line which differentiates in culture to form multinucleate myotubes. The regulation of the levels of cAMP-dependent protein kinases during myogenesis in L6 was studied, as these enzymes have been proposed to be involved in the control of this process. Measurement of the mRNA levels for the type I regulatory subunit (R{dollar}\sb{lcub}\rm I{rcub}{dollar}) of cAMP-dependent protein kinase, and studies on the rates of transcription from the gene coding for this protein, showed that the increase in R{dollar}\sb{lcub}\rm I{rcub}{dollar} which occurs during myogenesis is is not regulated transcriptionally. Measurement of R{dollar}\sb{lcub}\rm I{rcub}{dollar} half-lives showed that a decrease in the rate of R{dollar}\sb{lcub}\rm I{rcub}{dollar} degradation during myogenesis probably causes its increase. Studies on the regulation of the catalytic subunit (C) of cAMP-dependent protein kinase showed that the increase in this subunit, which also occurs during myogenesis, is probably regulated at the level of transcription, and not by a change in its rate of degradation. On the basis of these results it is proposed that the increase in R{dollar}\sb{lcub}\rm I{rcub}{dollar} during myogenesis is due to a decrease in its proteolysis caused by an increase in the amount of C available to bind with it. This type of mechanism may have relevance to the regulation of increases in other multisubunit complexes during differentiation.;The regulation of R{dollar}\sb{lcub}\rm I{rcub}{dollar} was also studied in a spontaneously-transformed L6 cell line which is unable to differentiate. Measurement of R{dollar}\sb{lcub}\rm I{rcub}{dollar} degradation rates in this cell line showed that R{dollar}\sb{lcub}\rm I{rcub}{dollar} proteolysis is altered in the presence of certain types of cAMP analogues. As R{dollar}\sb{lcub}\rm I{rcub}{dollar} from this cell line and normal L6 appeared to be structurally the same, it is proposed that a change in some protease accounts for the altered R{dollar}\sb{lcub}\rm I{rcub}{dollar} degradation. This change in proteolysis was not a common feature of myoblast transformation, as it was not observed in L6 myoblasts transformed by transfection of the Ha-ras oncogene.



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