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Type: Journal article
Title: A point mutant of human sphingosine kinase 1 with increased catalytic activity
Author: Pitson, S.
Moretti, P.
Zebol, J.
Vadas, M.
D'Andrea, R.
Wattenberg, B.
Citation: FEBS Letters, 2001; 509(2):169-173
Publisher: Elsevier Science BV
Issue Date: 2001
ISSN: 0014-5793
Abstract: Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate, a lipid second messenger that has been implicated in mediating such fundamental biological processes as cell growth and survival. Very little is currently known regarding the structure or mechanisms of catalysis and activation of SK. Here we have tested the functional importance of Gly(113), a highly conserved residue of human sphingosine kinase 1 (hSK), by site-directed mutagenesis. Surprisingly, a Gly(113)-->Ala substitution generated a mutant that had 1.7-fold greater catalytic activity than wild-type hSK (hSK(WT)). Our data suggests that the Gly(113)-->Ala mutation increases catalytic efficiency of hSK, probably by inducing a conformational change that increases the efficiency of phosphoryl transfer. Interestingly, hSK(G113A) activity could be stimulated in HEK293T cells by cell agonists to a comparable extent to hSK(WT).
Keywords: Humans; Sphingosine; Phosphotransferases (Alcohol Group Acceptor); Alanine; Aspartic Acid; Glycine; Mutagenesis, Site-Directed; Enzyme Stability; Enzyme Activation; Amino Acid Sequence; Conserved Sequence; Protein Folding; Point Mutation
RMID: 0020011655
DOI: 10.1016/S0014-5793(01)03162-3
Appears in Collections:Molecular and Biomedical Science publications

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