Search results for SPHK1

Showing 11 results out of 11

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Protein (2 results from a total of 2)

Identifier: R-HSA-391267
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: SPHK1: Q9NYA1
Identifier: R-HSA-5218716
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: SPHK1: Q9NYA1

Interactor (1 results from a total of 1)

Identifier: Q9NYA1-2
Species: Homo sapiens
Primary external reference: UniProt: Q9NYA1-2

Reaction (7 results from a total of 7)

Identifier: R-HSA-428273
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane
The cytosolic enzyme sphingosine kinase 1 (SPHK1) catalyzes the phosphorylation of sphingosine (SPG) to sphingosine 1-phosphate (S1P) (Nava et al. 2000, Pitson et al. 2000).
Identifier: R-HSA-9625814
Species: Homo sapiens
Compartment: plasma membrane
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).
Identifier: R-HSA-5218845
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane
Membrane-bound sphingosine (SPG) in cells attenuates basal Ras activity by stimulating the activity of Ras GTPase-activating proteins (RasGAPs). Upon its phosphorylation by SPHK1, SPG is converted to sphingosine 1-phosphate (S1P) which then displaces from GAP downregulating RASA1 (p120GAP) activity and thereby induces Ras-GTP accumulation. This overall increases the level of activated Ras-GTP leading to activation of the ERK/mitogen-activated protein kinase (MAPK) pathway and cell division (Shu et al. 2002, Wu et al. 2003, Spiegel & Milstien 2006).
Identifier: R-HSA-5218823
Species: Homo sapiens
Compartment: plasma membrane, cytosol
VEGF mediated activation of ERK1/2 depends on the activity of PKC. Sphingosine kinase 1 (SPHK1) has been identified as the connecting link between PKC and Ras activation. Activated SPHK1 does not activate Ras-GEF directly but rather modulates Ras-GAP activity to favour Ras activation. VEGF-mediated stimulation of SPHK1 results from the direct phosphorylation of SPHK1 by PKC (Shu et al. 2002). S225 in SPHK1 may be the target site of phosphorylation (Piston et al. 2003).
Identifier: R-HSA-9695949
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane
The cytosolic enzyme sphingosine kinase 2 (SPHK2) catalyzes the phosphorylation of sphingosine (SPG) to sphingosine 1-phosphate (S1P) (Liu et al. 2000). In contrast to pro-survival SPHK1, the BH3-only protein SPHK2 inhibits cell growth and enhances apoptosis (Maceyka et al. 2005).
Identifier: R-HSA-428214
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane
SPHK1 and 2 (sphingosine kinases 1 and 2) each catalyze the reaction of sphinganine (dihydrosphingosine) and ATP to form dihydrosphingosine 1-phosphate and ADP. Both enzymes are found in the cytosol (although they are also present in membrane-associated forms). Both enzymes also catalyze the phosphorylation of sphingosine to sphingosine 1-phosphate (S1P) (Liu et al. 2000, Nava et al. 2000, Pitson et al. 2000).
Identifier: R-HSA-8865994
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Phosphorylated tyrosine residues Y627 and Y659 of GAB1 serve as docking sites for the N-terminal and C-terminal SH2 domains of PTNP11 (SHP2), respectively, thus recruiting PTNP11 to the activated MET receptor (Schaeper et al. 2000, Cunnick et al. 2001). During mouse embryonic development, Gab1-mediated recruitment of Ptpn11 is crucial for Met receptor-directed placental development and migration of muscle progenitor cells to the limbs (Schaeper et al. 2007). PTPN11 is phosphorylated in response to HGF treatment, although phosphorylation sites and direct MET involvement have not been examined (Duan et al. 2006). Phosphorylation of PTPN11 at tyrosine residues Y542 and Y580 of splicing isoform 2 (matching Y546 and Y584 of PTPN11 splicing isoform 1) is required for PTPN11 phosphatase activity and for the recruitment of downstream effectors, such as GRB2 (Lu et al. 2001). Phosphorylation of PTPN11 in response to HGF treatment is required for the recruitment and activation of sphingosine kinase SPHK1, which may play a role in HGF-induced cell scattering (Duan et al. 2006). While PTPN11 promotes MAPK3/1 (ERK1/2) signaling downstream of MET, it can also dephosphorylate MET on unidentified tyrosine residues (Furcht et al. 2014).

Pathway (1 results from a total of 1)

Identifier: R-HSA-8865999
Species: Homo sapiens
PTPN11 (SHP2), recruited to activated MET receptor through GAB1, is phosphorylated in response to HGF treatment, although phosphorylation sites and direct MET involvement have not been examined (Schaeper et al. 2000, Duan et al. 2006). Phosphorylation of PTPN11 in response to HGF treatment is required for the recruitment and activation of sphingosine kinase SPHK1, which may play a role in HGF-induced cell scattering (Duan et al. 2006). While PTPN11 promotes MAPK3/1 (ERK1/2) signaling downstream of MET, it can also dephosphorylate MET on unidentified tyrosine residues (Furcht et al. 2014).
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