Isozymes of cyclic AMP-dependent protein kinases (PKA) in human lymphoid cell lines: Levels of endogenous cAMP influence levels of PKA subunits and growth in lymphoid cell lines
✍ Scribed by Bjørn Steen Skålhegg; Ann Kirsti Johansen; Finn Olav Levy; Kristin Brevik Andersson; Einar Martin Aandahl; Heidi Kiil Blomhoff; Vidar Hansson; Kjetil Taskén
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 337 KB
- Volume
- 177
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
Activation of the cAMP signaling pathway in lymphoid cells is known to inhibit cell proliferation of T and B cells as well as cytotoxicity of natural killer (NK) cells. In order to find suitable model systems to study cAMP-mediated processes, we have examined the expression of cAMP-dependent protein kinase (PKA), endogenous levels of cAMP, and cell proliferation in eight cell lines of B lineage origin, four cell lines of T lineage origin, and normal human B and T cells. We demonstrated that the expression of mRNA and protein for one of the regulatory (R) subunits of PKA (RIa) was present in all the cells investigated, in contrast to the other R subunits (RIb, RIIa, and RIIb). Furthermore, three T cell lines and one B cell line expressed only RIa and C, implying these cells to contain solely PKA type I. Moreover, for the RI subunit, we observed an apparent reciprocal relationship between levels of mRNA and protein. Generally, RIa protein was low in cell lines where mRNA was elevated and vice versa. This was not the case for the RII subunits, where high levels of mRNA were associated with elevated levels of protein. Interestingly, we demonstrated an inverse correlation between levels of endogenous cAMP and cell growth as determined by [ 3 H]thymidine incorporation and cell-doubling rate (P õ 0.05). Taken together, our results demonstrate great differences in PKA isozyme composition, which should be taken into consideration when using lymphoid cell lines as model system for cAMP/PKA effects in normal lymphocytes.