SPHK1 phosphorylates sphingosine in response to E2 stimulation

Stable Identifier
Reaction [transition]
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
11185956 Sphingosine 1-phosphate activates Erk-1/-2 by transactivating epidermal growth factor receptor in rat-2 cells

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

IUBMB Life 2000
24530924 Estrogen biology: new insights into GPER function and clinical opportunities

Prossnitz, ER, Barton, M

Mol. Cell. Endocrinol. 2014
12588983 Identification of a structural determinant necessary for the localization and function of estrogen receptor alpha at the plasma membrane

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

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

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

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

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

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

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
Catalyst Activity

D-erythro-sphingosine kinase activity of SPHK1 [cytosol]

This event is regulated
Orthologous Events
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