Reactome | SPHK1 phosphorylates sphingosine in response to E2 stimulation

SPHK1 phosphorylates sphingosine in response to E2 stimulation

Stable Identifier

R-HSA-9625814

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

SPHK1 phosphorylates sphingosine in response to E2 stimulation

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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