Cellular Gangliosides Promote Growth Factor-induced Proliferation of Fibroblasts

作者: Ruixiang Li , Jessica Manela , Yu Kong , Stephan Ladisch

DOI: 10.1074/JBC.M906368199

关键词: GangliosideGrowth factorFibroblast growth factorReceptor tyrosine kinaseCell growthBiologyCell biologyCeramideGrowth factor receptor inhibitorCeramide synthase

摘要: Abstract Cell surface gangliosides have been proposed as modulators of transmembrane signaling. In this study, we used two complementary approaches to investigate the function cellular in response mammalian fibroblasts growth factors. First, inhibition glucosyl ceramide synthase by a new specific inhibitor ofd-l-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol-HCl (glucosylceramide synthase), which depletes at concentration 1 μm without causing an increase levels, blocked epidermal factor-stimulated proliferation fibroblasts. Similarly, responses several other factors that activate receptor tyrosine kinases, including fibroblast factor, insulin-like factor-I, and platelet-derived were inhibited 50–100%. Conversely, enrichment preincubation mouse human with exogenously added enhanced factor-elicited cell proliferation. Novel findings distinguishing it from previous similar studies, include differential effects versus continuous incubation cells on factor-dependent factor-like action NeuNAc α2–3Galβ1–3GalNAcβ1–4(NeuNAcα2–3)Galβ1–4Glcβ1–1Cer when are pretreated ganglioside.

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