SPHK1 phosphorylates sphingosine in response to E2 stimulation

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R-HSA-9625814
Type
Reaction [transition]
Species
Homo sapiens
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Estrogen stimulation of breast cancer cells promotes ESR1- dependent activation of sphingosine kinase 1 (SPHK1) (Sukocheva et al, 2003; Sukhocheva et al, 2006). SPHK1 catalyzes the formation of sphingosine-1-phosphate (S1P) , a ligand for the GPCR S1PR3 receptor, also known as EDG3 (Hla et al, 2001; Spiegel and Milstein, 2003; Sukocheva et al, 2006). S1P-bound S1PR3 stimulates EGFR transactivation downstream of estradiol stimulation through the MMP-dependent release of HBEGF from the plasma membrane, leading to EGFR and MAPK phosphorylation (Kim et al, 2000; Tanimoto et al, 2004; Filardo et al, 2000; Razandi et al, 2003; Sukocheva et al, 2003; Sukocheva et al, 2006; reviewed in Prossnitz and Barton, 2014).

Literature References
PubMed ID Title Journal Year
24530924 Estrogen biology: new insights into GPER function and clinical opportunities

Prossnitz, ER, Barton, M

Mol. Cell. Endocrinol. 2014
11185956 Sphingosine 1-phosphate activates Erk-1/-2 by transactivating epidermal growth factor receptor in rat-2 cells

Kim, JH, Kim, J H, Song, WK, Kim, J H, Chun, JS

IUBMB Life 2000
12588983 Identification of a structural determinant necessary for the localization and function of estrogen receptor alpha at the plasma membrane

Razandi, M, Alton, G, Pedram, A, Ghonshani, S, Webb, P, Levin, ER

Mol. Cell. Biol. 2003
16636149 Estrogen transactivates EGFR via the sphingosine 1-phosphate receptor Edg-3: the role of sphingosine kinase-1

Sukocheva, O, Wadham, C, Holmes, A, Albanese, N, Verrier, E, Feng, F, Bernal, A, Derian, CK, Ullrich, A, Vadas, MA, Xia, P

J. Cell Biol. 2006
12881510 Sphingosine kinase transmits estrogen signaling in human breast cancer cells

Sukocheva, OA, Wang, L, Albanese, N, Pitson, SM, Vadas, MA, Xia, P

Mol. Endocrinol. 2003
11043579 Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF

Filardo, EJ, Quinn, JA, Bland, KI, Frackelton, AR

Mol. Endocrinol. 2000
15044318 Sphingosine 1-phosphate transactivates the platelet-derived growth factor beta receptor and epidermal growth factor receptor in vascular smooth muscle cells

Tanimoto, T, Lungu, AO, Berk, BC

Circ. Res. 2004
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Catalyst Activity
Title
D-erythro-sphingosine kinase activity of SPHK1 [cytosol]
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