Sphingosine and FTY720 directly bind pro-survival 14-3-3 proteins to regulate their function

Woodcock, Joanna M.; Ma, Yuefang; Coolen, Carl; Pham, Duyen; Jones, Claire F.; Lopez, Angel F.; Pitson, Stuart M.

doi:10.1016/j.cellsig.2010.04.004

Cited by 72 publications

(72 citation statements)

References 25 publications

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“…Phosphorylation of 14-3-3 induced by FTY720 could facilitate, at least in part, the apoptotic activity of this drug, as cells expressing nonphosphorylatable 14-3-3 exhibited attenuated apoptosis in response to FTY720 (98). Therefore, 14-3-3 proteins are key intermediates linking FTY720 and mitochondria, apoptotic commitment.…”

Section: Sphingosine Kinase (Sphk)mentioning

confidence: 99%

FTY720 for cancer therapy (Review)

Zhang

Wang

et al. 2013

Oncology Reports

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Abstract. 2-Amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride (FTY720) is a potent immunosuppressant which has been approved by the Food and Drug Administration (FDA) as a new treatment for multiple sclerosis. As an immunosuppressant, it displays its anti-multiple sclerosis, immunosuppressive effects by activating sphingosine-1-phosphate receptors (S1PRs). In addition to the immunosuppressive effects, FTY720 also shows preclinical antitumor efficacy in several cancer models. In most cases, phosphorylation of FTY720 is not required for its cytotoxic effect, indicating the involvement of S1PR-independent mechanisms which are starkly different from the immunosuppressive property of FTY720. In the present study, we reviewed the rapidly advancing field of FTY720 in cancer therapy as well as some molecular targets of the unphosphorylated form of FTY720.

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Section: Sphingosine Kinase (Sphk)mentioning

confidence: 99%

FTY720 for cancer therapy (Review)

Zhang

Wang

et al. 2013

Oncology Reports

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“…15 As the functions of 14-3-3s depend on their dimeric structure, 16,17 sphingosine might induce apoptosis through induction of 14-3-3 monomerization, 5,18 however, to the best of our knowledge, the involvement of this sphingosine-dependent mechanism in the dissociation of 14-3-3s from proapoptotic mediators has never been demonstrated.…”

mentioning

confidence: 95%

“…Given the importance of 14-3-3 phosphorylation at Ser58 for initiation of apoptosis by sphingosine in animal cells, 5 we examined whether Arabidopsis 14-3-3s might also be phosphorylated in response to PHS. The Ser58 phosphorylation site in the human isoform 14-3-3z and the primary sequence surrounding it are highly conserved in yeast and plant 14-3-3 proteins (Supplementary Figure S1).…”

Section: Phs Induces Calcium-dependent Pcdmentioning

confidence: 99%

“…11 Recently, it has been shown that sphingosine allows phosphorylation of 14-3-3z on a specific serine residue (Ser58). 5 Sphingosine-dependent phosphorylation of 14-3-3z at Ser58 can be catalysed by two different protein kinases, namely sphingosine-dependent kinase 1 (SDK1), identified as the caspase-cleaved fragment of protein kinase C (PKC)d, 12,13 and protein kinase A (PKA).…”

mentioning

confidence: 99%

“…Recently, direct binding of this LCB to 14-3-3 proteins was shown to control cell fate. 5 The 14-3-3 proteins are a family of highly conserved proteins that have central regulatory roles in eukaryotes. 6 14-3-3s Function as homoand heterodimers that bind phosphopeptide motifs in diverse target proteins.…”

mentioning

confidence: 99%

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14-3-3-Regulated Ca2+-dependent protein kinase CPK3 is required for sphingolipid-induced cell death in Arabidopsis

et al. 2012

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In eukaryotic cells, sphingoid long chain bases (LCBs) such as sphingosine or phytosphingosine (PHS) behave as second messengers involved in various processes including programmed cell death (PCD). In plants, induction of PCD by LCBs has now been described, but the signalling pathway is still enigmatic. Using Arabidopsis, we identify new key steps in this pathway. We demonstrate that PHS induces activation of the calcium-dependent kinase CPK3, which phosphorylates its binding partners, the 14-3-3 proteins. This phosphorylation leads to the disruption of the complex and to CPK3 degradation. Using cpk3 knockout lines, we demonstrate that CPK3 is a positive regulator of LCB-mediated PCD. These findings establish 14-3-3-regulated CPK3 as a key component of the LCB pathway leading to PCD in plants.

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