Decreased adenylate cyclase responsiveness of transformed cells correlates with the presence of a viral transforming protein

Abstract

The adenylate cyclase responsiveness of transformed fibroblastic and epithelial cell lines to forskolin, fluoride, guanine nucleotides and cholera toxin was reduced compared to their parental counterparts. This phenomenon was observed in lines transformed by either RNA or DNA tumor viruses, and in the case of polyoma virus, coincided with the expression of middle T antigen. The data suggest that decreased responsiveness of adenylate cyclase to non-hormone activators is a general consequence of viral transformation and may be related to viral regulation of protein kinase activity.

Protein kinase C and a viral K‐RAS protein cooperatively enhance the response of adenylate cyclase to stimulators

“…However, it is also apparent from their studies that the responsiveness (i.e., the fold increase over basal activity) of adenylate cyclase to stimulation was significantly higher in ras-transformed cells than in the corresponding untransformed cells. Thus, in this regard, the data of Beckner (1984) and Chiarugi et al (1985) are consistent with both the present observations and those of Franks et al (1987a,b) and KonishiImamura et al (1987). The viral K-rus protein strikingly increases the stimulation of membrane-associated PKC activity by TPA without affecting the TPA-induced redistribution of the enzyme from the soluble cytosol to the detergentextractable membrane fraction.…”

“…At first sight, the demonstration that a viral K-ras protein can increase the responsiveness of adenylate cyclase in tsKSV-NRK cells to IPR and PGEl as well as earlier demonstrations that the viral K-ras proteins increase the responsiveness of NRK and NIH-3T3 cell adenylate cyclase to cholera toxin, GTP-analogs, forskolin, and sodium fluoride (Franks et al, 1987a,b;Konishi-Imamura et al, 1987) might seem to contra- dict the observations of others. Beckner (1984) and Chiarugi et al (1985) concluded that transformation by viral H-rus or K-rus proteins reduced the responsiveness of adenylate cyclase to cholera toxin, forskolin, IPR, PGE1, and sodium fluoride. These conclusions were based on the fact that basal adenylate cyclase activity was reduced in cells following rus transformation and that upon stimulation the levels of activity never reached those levels seen in stimulated untransformed cells.…”

Dibutyryl cAMP inhibits expression of transformation-related properties in Kirsten murine sarcoma virus transformed Balb/c-3T3 cells despite continued presence of p21v-Ki-ras

“…Ki-MSV and Ha-MSV transformants exhibit reduced adenylate cyclase activity and reduced intracellular levels of CAMP (Carchman et al 1974;Anderson and Pastan 1975;Beckner 1984). Attempts to use purified Ha-MSV p21 to restore adenylate cyclase activity to plasma membranes in cells lacking the stimulatory G protein of adenylate cyclase have been unsuccessful (Beckner et al 1985).…”