Inhibition of the insulin receptor tyrosine kinase by sphingosine.

摘要: Sphingosine inhibits autophosphorylation of the insulin receptor tyrosine kinase in vitro and situ. This lysosphingolipid has been shown previously to inhibit Ca2+/lipid-dependent protein C. Here we show that insulin-dependent partially purified is half-maximally inhibited by 145 microM sphingosine (9 mol %) Triton X-100 micelles. Half-maximal inhibition C occurs with 60 (3.4 mixed micelles containing phosphatidylserine diacylglycerol. Sphingomyelin does not significantly receptor, suggesting that, as C, free amino group may be essential for inhibition. Similar effects observed reduced presence other lipids. However, reduction displays a marked dependence on lipid species: phosphatidylserine, but mixture lipids compositionally similar cell membrane, markedly reduces potency The at level protein/membrane interaction: soluble form comprising cytoplasmic domain resistant Lastly, insulin-stimulated rate phosphorylation NIH 3T3 cells expressing human receptor. These results suggest alters membrane function independently