L-serine potentiates the mitogenic effects of growth factors on cultured human keratinocytes.

L-Serine increased the growth of passaged human foreskin keratinocytes in terms of DNA and protein per dish of cells, and potentiated the mitogenic effects of serum and epidermal growth factor, and also insulin, keratinocyte growth factor, and a bovine pituitary extract. The effects of serine were apparent with as little as 0.05 mM. The stimulatory effects of these various growth factors were additive, without synergism. Exposure to L-[3H]serine resulted in labeling of the phospholipids phosphatidyl (Ptd) serine, Ptd ethanolamine, sphingomyelin, and, to a slight extent, Ptd choline. The time course of labeling suggested synthesis of Ptd serine was initiated; Ptd serine was converted to Ptd ethanolamine; little methylation of Ptd ethanolamine to form Ptd choline took place. Separation of nonradioactive phospholipids and phosphorus assay of individual lipids showed that serine-supplemented cells had only slightly increased content of Ptd serine and Ptd ethanolamine. The significance of these for activation of protein kinase C is discussed.