Enhancement of sphingosine kinase 1 catalytic activity by deletion of 21 amino acids from the COOH-terminus

Jeremy Hengst, Jacquelyn M. Guilford, Elizabeth J. Conroy, Xujun Wang, Jong Yun

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Sphingosine kinase 1 (SphK1) responds to a variety of growth factor signals by increasing catalytic activity as it translocates to the plasma membrane (PM). Several studies have identified amino acids residues involved in translocation yet how SphK1 increases its catalytic activity remains to be elucidated. Herein, we report that deletion of 21 amino acids from the COOH-terminus of SphK1 (1-363) results in increased catalytic activity relative to wild-type SphK1 (1-384) which is independent of the phosphorylation state of Serine 225 and PMA stimulation. Importantly, HEK293 cells stably expressing the 1-363 protein exhibit enhanced cell growth under serum-deprived cell culture conditions. Together the evidence indicates that the COOH-terminal region of SphK1 encompasses a structural element that is necessary for the increase in catalytic activity in response to PMA treatment and that its deletion renders SphK1 constitutively active with respect to PMA treatment.

Original languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume494
Issue number1
DOIs
StatePublished - Feb 1 2010

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Catalyst activity
Amino Acids
Phosphorylation
HEK293 Cells
Cell growth
Cell membranes
Cell culture
Serine
sphingosine kinase
Intercellular Signaling Peptides and Proteins
Cell Culture Techniques
Cell Membrane
Growth
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

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abstract = "Sphingosine kinase 1 (SphK1) responds to a variety of growth factor signals by increasing catalytic activity as it translocates to the plasma membrane (PM). Several studies have identified amino acids residues involved in translocation yet how SphK1 increases its catalytic activity remains to be elucidated. Herein, we report that deletion of 21 amino acids from the COOH-terminus of SphK1 (1-363) results in increased catalytic activity relative to wild-type SphK1 (1-384) which is independent of the phosphorylation state of Serine 225 and PMA stimulation. Importantly, HEK293 cells stably expressing the 1-363 protein exhibit enhanced cell growth under serum-deprived cell culture conditions. Together the evidence indicates that the COOH-terminal region of SphK1 encompasses a structural element that is necessary for the increase in catalytic activity in response to PMA treatment and that its deletion renders SphK1 constitutively active with respect to PMA treatment.",
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Enhancement of sphingosine kinase 1 catalytic activity by deletion of 21 amino acids from the COOH-terminus. / Hengst, Jeremy; Guilford, Jacquelyn M.; Conroy, Elizabeth J.; Wang, Xujun; Yun, Jong.

In: Archives of Biochemistry and Biophysics, Vol. 494, No. 1, 01.02.2010, p. 23-31.

Research output: Contribution to journalArticle

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