Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation

Figure 3

Intracellular SK-1 and SK-2 activity. The activation of SK-1 and SK-2 occurs via ERK1/2 phosphorylation in response to proinflammatory mediators, such as histamine and TNFα. Upon the activation, SK-1 is translocated from the cytoplasm to plasma membrane where it catalyses sphingosine to form S1P. S1P can then be transported outside the cell and then act back on its receptors to induce the activation of G-proteins for subsequent cellular changes, such as survival, proliferation, and migration. In contrast, SK-2 activity is associated primarily with the nuclear membrane, where it is phosphorylated prior to being translocated out of the nucleus. At the nuclear membrane and endoplasmic reticulum, S1P can be dephosphorylated to sphingosine and ceramide via the sphingolipid salvage pathway where many enzymes including sphingomyelinases, cerebrosidases, ceramides, and ceramide synthases are involved to induce apoptosis.