2010
DOI: 10.1038/onc.2010.420
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Guanine nucleotides regulate sphingosine kinase 1 activation by eukaryotic elongation factor 1A and provide a mechanism for eEF1A-associated oncogenesis

Abstract: Sphingosine kinase 1 (SK1) catalyses the formation of bioactive phospholipid sphingosine 1-phosphate (S1P). Elevated cellular SK1 activity and S1P levels enhance cell proliferation and survival, and are strongly implicated in tumourigenesis. Regulation of SK1 activity can occur through various mechanisms, including phosphorylation and protein-protein interactions. We have previously shown that eukaryotic elongation factor 1A (eEF1A) interacts with and directly activates SK1, but the mechanisms regulating this … Show more

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Cited by 43 publications
(37 citation statements)
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“…The above studies linking high levels of SK with enhancement of viral infection are in contrast to our own observations of a reduction in SK1 activity in response to dengue virus (DENV) infection (Wati et al, 2011), as also reported for the related flavivirus bovine viral diarrhea virus (Yamane et al, 2009). Close analysis of the time-course of the reduction in SK1 in DENV-infected cells demonstrates a correlation with high levels of the DENV 39 UTR, which can compete for the SK1 activator eEF1A (Carr et al, 2013a;Leclercq et al, 2008Leclercq et al, , 2011, which is utilized by flaviviruses to assist replication (Blackwell & Brinton, 1997;Davis et al, 2007). Additionally, our previous data (Carr et al, 2013a;Calvert et al, 2015), as well as that of Yamane et al (2009), suggest an increase in SK1 activity in the early hours following infection.…”
Section: Introductionsupporting
confidence: 56%
“…The above studies linking high levels of SK with enhancement of viral infection are in contrast to our own observations of a reduction in SK1 activity in response to dengue virus (DENV) infection (Wati et al, 2011), as also reported for the related flavivirus bovine viral diarrhea virus (Yamane et al, 2009). Close analysis of the time-course of the reduction in SK1 in DENV-infected cells demonstrates a correlation with high levels of the DENV 39 UTR, which can compete for the SK1 activator eEF1A (Carr et al, 2013a;Leclercq et al, 2008Leclercq et al, , 2011, which is utilized by flaviviruses to assist replication (Blackwell & Brinton, 1997;Davis et al, 2007). Additionally, our previous data (Carr et al, 2013a;Calvert et al, 2015), as well as that of Yamane et al (2009), suggest an increase in SK1 activity in the early hours following infection.…”
Section: Introductionsupporting
confidence: 56%
“…Also a truncated form of eEF1A, termed prostate tumor inducer-1 (PTI-1), which lacks the G-protein domain and cannot bind GTP, retains its ability to activate SphK1 activity. PTI-1 induced neoplastic transformation of NIH3T3 cells, which is blocked by the inhibition of SphK1 [259]. This unexpected activation of SphK1 by eEF1A may be important in cancer cells since the activation of SphK1 is essential for its oncogenic abilities [260].…”
Section: Eef1a-mediated Activation Of Sphk1mentioning
confidence: 90%
“…eEF1A1 is a highly conserved GTP-binding protein in eukaryotic cells that plays a significant role in peptide chain extension during protein synthesis (14). Research indicates that eEF1A1 plays an important role in the regulation of various biological characteristics of cells, such as the cell cycle, cell growth, and cell death (16,17). Studies have shown that eEF1A1 is aberrantly upregulated in many tumor tissues (18,19).…”
Section: Introductionmentioning
confidence: 99%