Polyphosphoinositide metabolism is rapidly stimulated by activation of a temperature-sensitive mutant of Rous sarcoma virus in rat fibroblasts.
We have examined polyphosphoinositide turnover in a Rat-1 fibroblast line infected with a temperature-sensitive mutant (ts LA24) of the Rous sarcoma virus (RSV). When ts LA24-infected cells are shifted from the non-permissive to the permissive temperature, a rapid and sustained activation of phospholipase C (PLC) is observed. Normal and wild-type RSV-infected Rat-1 cells do not show any PLC activation upon temperature shiftdown. Pre-treatment of ts LA24-infected fibroblasts with tetrodotoxin (a Na+ channel inhibitor) or incubation in Na+-free medium significantly prevent temperature shiftdown-induced PLC activation. Therefore, we conclude that PLC activation occurs concomitantly with pp60v-src expression, and hypothesize that pp60v-src-related membrane depolarization is the causal link between pp60v-src tyrosine kinase activity and stimulation of polyphosphoinositide metabolism. Finally, we discuss the relationship between the phenomena we have observed and the mechanism of action of the ras oncogene.
Chiarugi
V
V
Laboratory of Molecular Biology, Istituto di Patologia Generale, Firenze, Italy.
Porciatti
F
F
Pasquali
F
F
Magnelli
L
L
Giannelli
S
S
Ruggiero
M
M
D000818:Animals; D002460:Cell Line; D007295:Inositol Phosphates / Q000378:metabolism; D008564:Membrane Potentials; D015688:Oncogene Protein pp60(v-src); D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D012191:Retroviridae Proteins / Q000502:physiology*; D013696:Temperature; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D012191:Retroviridae Proteins; D015688:Oncogene Protein pp60(v-src); D010738:Type C Phospholipases