Stimulation of sensitive EL4 mouse thymoma cells (s-EL4) with phorbol esters results in production of interleukin 2 (IL-2), adherence to a plastic substrate, and growth inhibition, whereas a phorbol ester-resistant variant (r-EL4) fails to respond. Previous studies revealed substantially decreased expression of protein kinase C (PKC) ε in the r-EL4 versus s-EL4 cells. This work has been extended to examine the more recently described PKC isozymes. Western and Northern analyses revealed a marked decrease in PKC η and ϑ in r-EL4 as compared to s-EL4 cells. Treatment of these lines with phorbol ester for 24 h resulted in down-regulation of all PKC isozymes examined except PKC η, which was up-regulated in the s-EL4 cells at the time of maximal IL-2 production. Two newly isolated EL4 clones, resistant to phorbol ester-induced growth inhibition but still exhibiting the phorbol ester-induced adherence and IL-2 production, both expressed PKC η and ϑ. Collectively, these observations suggest a dissociation of growth inhibition from adherence and IL-2 production pathways and a potential role for PKC η in the latter.


This work was supported by DHHS (Department of Health and Human Services) Grant GM31184. M. S. R. was supported in part by DHHS Pharmacological Sciences Training Grant T32 GM07055.

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