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Roles, regulation and inhibitors of sphingosine kinase 2
Author(s) -
Neubauer Heidi A.,
Pitson Stuart M.
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12314
Subject(s) - sphingosine , sphingolipid , ceramide , sphingosine kinase , sphingosine kinase 1 , sphingosine 1 phosphate , biology , lipid signaling , microbiology and biotechnology , kinase , carcinogenesis , cancer research , cancer , apoptosis , biochemistry , enzyme , genetics , receptor
The bioactive sphingolipids ceramide, sphingosine and sphingosine‐1‐phosphate (S1P) are important signalling molecules that regulate a diverse array of cellular processes. Most notably, the balance of the levels of these three sphingolipids in cells, termed the ‘sphingolipid rheostat’, can dictate cell fate, where ceramide and sphingosine enhance apoptosis and S1P promotes cell survival and proliferation. The sphingosine kinases ( SK s) catalyse the production of S1P from sphingosine and are therefore central regulators of the sphingolipid rheostat and attractive targets for cancer therapy. Two SK s exist in humans: SK 1 and SK 2. SK 1 has been extensively studied and there is a large body of evidence to demonstrate its role in promoting cell survival, proliferation and neoplastic transformation. SK 1 is also elevated in many human cancers which appears to contribute to carcinogenesis, chemotherapeutic resistance and poor patient outcome. SK 2, 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 SK 2 in key roles in a variety of diseases, including the development of a range of solid tumours. Here, we review the literature examining SK 2, its physiological and pathophysiological functions, the current knowledge of its regulation, and recent developments in targeting this complex enzyme.