PHOSPHOCHOLINE AND SPHINGOSINE-1-PHOSPHATE SYNERGISTICALLY STIMULATE DNA-SYNTHESIS BY A MAP KINASE-DEPENDENT MECHANISM

We have previously shown that in NIH 3T3 fibroblasts phosphocholine (P Cho) potentiates sphingosine-1-phosphate (S1P)-induced mitogenesis. He re we report that PCho and S1P also synergistically stimulate DNA synt hesis in mouse Swiss 3T3 fibroblasts and in mouse JB6 epidermal cells. The combined actions of PCho and S1P on DNA synthesis were associated with synergistic activation of the p42/p44 mitogen-activated protein (MAP) kinases. Ethanolamine (50-100 mu M) further enhanced the synergi stic effects of PCho and S1P on DNA synthesis but not on MAP kinase ac tivity. The results indicate that the synergistic mitogenic effects of PCho and S1P (i) are not restricted to NIH 3T3 fibroblasts, (ii) are predominantly mediated by the MAP kinase-dependent signal transduction pathway, and (iii) are enhanced by ethanolamine via a MAP kinase-inde pendent mechanism. (C) 1997 Federation of European Biochemical Societi es.