proapoptotic sphingosine (So) and ceramide (Cer). Thus, as central enzymes in modulating the Cer/S1P balance, SKs are attractive targets for cancer therapy ( 1 ). Two SKs exist in humans, SK1 and SK2. SK1 has been extensively studied and there is a large body of evidence that proves its role in promoting cell survival, proliferation, and neoplastic transformation ( 2-5 ). SK1 is also elevated in many human cancers, which appears to contribute to carcinogenesis, chemotherapeutic resistance, and poor patient outcome. SK2, however, has not been as well-characterized, and there are contradictions in the key physiological functions that have been proposed for this isoform. Despite this, many studies are now emerging that implicate SK2 in key roles in a variety of diseases, including the development of a range of solid tumors ( 6 ).The potential of SKs as therapeutic targets has boosted the development of small molecule inhibitors ( 4,(7)(8)(9)(10)(11)(12)(13)(14). A detailed characterization of their pharmacology, particularly their selectivity against human SK1 and SK2, has been published ( 15 ). The fi rst known SK inhibitors were long chain base analogs such as N , N -dimethyl-D-erythro-sphingosine (DMS) ( 16,17 ) and L-threo-dihydrosphingosine (safi ngol) ( 18-21 ). While DMS inhibits both SK1 and SK2 by (SGR 2009(SGR 1072, and the Fundació la Marató de TV3 (112130 and 112132 Abbreviations: CB5R, NADH-cytochrome b5 reductase; C16dhCer, N -hexadecanoyldihydrosphingosine ; CDH, ceramide dihexoside (lactosylceramide); Cer, ceramide; CerC6NBD, N -[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-sphingosine; CMH, ceramide monohexoside (glucosyl and galactosylceramide); Des1, dihydroceramide desaturase; dhCDH, dihydroceramide dihexoside (lactosyldihydroceramide); dhCer, dihydroceramide; dhCerC6NBD, N -[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-dihydrosphingosine; dhSM, dihydrosphingomyelin; DMS, N , N -dimethyl-D-erythro-sphingosine; FAD, fl avin adenine dinucleotide; LC3, microtubule-associated protein 1-light chain 3; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; NBD, 4-nitro-2,1,3-benzoxadiazole; PDB, Protein Data Bank; S1P, sphingosine-1-phosphate; SK, sphingosine kinase; SKI, sphingosine kinase inhibitor; So, sphingosine; TBST, TBS with 0.1% Tween 20; UPLC, ultraperformance LC . This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2011-22444), the Generalitat de Catalunya

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New fluorogenic sensors with suitable kinetic parameters and sensitivity have been developed for the determination of sphingosine-1-phosphate lyase activity in cell lysates. The probe RBM148 can be efficiently loaded into cationic liposomes and used to determine S1PL activity in intact cells.