REGULATION OF CASEIN KINASE-II BY GROWTH-FACTORS - A REEVALUATION

Many of the effects of growth factors or hormones are mediated through the activation of protein kinase cascades. In this regard, it is well established that the activity of several protein kinases can be drama tically increased when cells are treated with a variety of stimuli. Si nce 1987, there have been several reports demonstrating that the activ ity of casein kinase II (CKII) can be acutely increased by hormones or growth factors. However, there are a number of discrepancies regardin g the activation of CKII. In this study, we have examined CKII activit ies in extracts prepared from cells following treatment with stimuli t hat had been previously shown to elicit dramatic increases in CKII act ivity. Human WI.38 diploid lung fibroblasts were stimulated with serum or a variety of other stimuli including insulin, platelet-derived gro wth factor, fibroblast growth factor, epidermal growth factor, or phor bol myristate acetate. Human A431 epidermal carcinoma cells were simil arly treated with epidermal growth factor. No reproducible increases i n CKII activity were observed in response to any of these treatments. By comparison, a dramatic increase in kinase activity towards a synthe tic peptide based on phosphorylation sites within the ribosomal S6 pro tein was consistently measured. Our observations indicate that CKII is not regulated in a similar manner by growth factors as are the protei n kinases of the MAP kinase cascade, e.g., MAP kinase itself or riboso mal protein S6 kinase.