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  • Title: Sphingosylphosphorylcholine activation of mitogen-activated protein kinase in Swiss 3T3 cells requires protein kinase C and a pertussis toxin-sensitive G protein.
    Author: Seufferlein T, Rozengurt E.
    Journal: J Biol Chem; 1995 Oct 13; 270(41):24334-42. PubMed ID: 7592645.
    Abstract:
    Sphingosylphosphorylcholine (SPC) is a potent mitogen for Swiss 3T3 cells, but the signaling mechanisms involved are poorly characterized. Here, we report that addition of SPC induces a rapid and transient activation of p42 mitogen-activated protein kinase (p42MAPK) in these cells. SPC-induced p42MAPK activation peaked at 5 min and was undetectable after 30 min of incubation with SPC. The effect of SPC on p42MAPK activation was comparable to that induced by bombesin and platelet-derived growth factor. As SPC strongly induced phosphorylation of the major protein kinase C (PKC) substrate 80K/MARCKS in either intact or permeabilized cells, we examined whether PKC could be involved in SPC-induced p42MAPK activation. Here, we demonstrate that p42MAPK activation by SPC was dependent on PKC activity as shown by inhibition of PKC with the bisindolymaleimide GF 109203X or down-regulation of PKC by prolonged treatment of Swiss 3T3 cells with phorbol esters. Activation of both PKC and p42MAPK by SPC was markedly inhibited by treatment with pertussis toxin, implicating a G proteins(s) of the Gi/G(o) subfamily in the action of SPC. SPC-induced rapid activation of a downstream target of p42MAPK, p90 ribosomal S6 kinase (p90rsk), also required PKC and a pertussis toxin-sensitive G protein. In addition, SPC-induced mitogenesis was dependent on a Gi protein in Swiss 3T3 cells. SPC also induced p42MAPK activation and DNA synthesis in secondary cultures of mouse embryo fibroblasts through a pertussis toxin-sensitive pathway. As G proteins link many cell surface receptors to effector proteins, we hypothesize, therefore, that SPC could bind to a receptor that mediates at least some of its biological effects in Swiss 3T3 cells and mouse embryo fibroblasts.
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