Sphingosine 1-phosphate (S1P) is a highly bioactive lipid that has a myriad of biological effects both intracellularly as a second messenger and extracellularly by binding to the S1P(1-5)/G-protein-coupled receptors of the endothelial differentiation gene family. Intracellularly, at least two enzymes, sphingosine kinase (1 and 2) and S1P phosphatase, regulate the activity of S1P by governing the phosphorylation of S1P. Regulation of hS1Pase1 with the resultant changes in cellular and secreted S1P has important implications in cell proliferation, angiogenesis and apoptosis.

Sphingosine-1-phosphate lyase cleaves phosphorylated sphingoid bases, such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis. The catalytic activity of sphingosine 1-phosphate lyase converts sphingosine 1-phosphate to phosphoethanolamine and palmitaldehyde using Pyridoxal phosphate as a co-factor. Sphingosine 1-phosphate lyase is a type III membrane protein found in the endoplasmic reticulum. Sphingosine 1-phosphate lyase is found primarily in the liver and kidney. Sphingosine 1-phosphate lyase belongs to the group II decarboxylase family.

EDG6 (S1P4) belongs to a family of G-protein coupled receptors whose ligands are lysophospholipids. The ligand for EDG6 (S1P4) is sphingosine 1-phosphate. There are 8 known members of the EDG receptor family and they are implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival and suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. They couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG6 (S1P4) is expressed in lymphoid and hematopoietic tissue and in the lungs. _x000B_

EDG6 (S1P4) belongs to a family of G-protein coupled receptors whose ligands are lysophospholipids. The ligand for EDG6 (S1P4) is sphingosine 1-phosphate. There are 8 known members of the EDG receptor family and they are implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival and suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. They couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG6 (S1P4) is expressed in lymphoid and hematopoietic tissue and in the lungs. _x000B_

EDG6 (S1P4) belongs to a family of G-protein coupled receptors whose ligands are lysophospholipids. The ligand for EDG6 (S1P4) is sphingosine-1-phosphate. There are 8 known members of the EDG receptor family and they are implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival and suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. They couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG6 (S1P4) is expressed in lymphoid and hematopoietic tissue and in the lungs. _x000B_Recently, the designation of the EDG receptors has been modified to include the ligand for the receptor. Thus, the new designation for the EDG6 (S1P4) receptor is the sphingosine 1-phosphate receptor-4 (S1P4).

EDG6 (S1P4) belongs to a family of G-protein coupled receptors whose ligands are lysophospholipids. The ligand for EDG6 (S1P4) is sphingosine-1-phosphate. There are 8 known members of the EDG receptor family and they are implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival and suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. They couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG6 (S1P4) is expressed in lymphoid and hematopoietic tissue and in the lungs. _x000B_Recently, the designation of the EDG receptors has been modified to include the ligand for the receptor. Thus, the new designation for the EDG6 (S1P4) receptor is the sphingosine 1-phosphate receptor-4 (S1P4).

EDG-6 belongs to a family of G-protein coupled receptors whose ligands are lysophospholipids. The ligand for EDG-6 is sphingosine-1-phosphate. There are 8 known members of the EDG receptor family and they are implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival and suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. They couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG-6 is expressed in lymphoid and hematopoietic tissue and in the lungs. _x000B_Recently, the designation of the EDG receptors has been modified to include the ligand for the receptor. Thus, the new designation for the EDG-6 receptor is the sphingosine 1-phosphate receptor-4 (S1P-4).

Endothelial cell differentation gene-3 (EDG3) belongs to a family of G-protein couple receptors whose ligands are lysophospholipids. The ligand for EDG3 is sphingosine-1-phosphate. There are 8 known members of the EDG receptor family. They have been implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. The couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG3 is expressed in cardiovascular, leukocyte-containing and other tissues.

Endothelial cell differentation gene-3 (EDG3) belongs to a family of G-protein couple receptors whose ligands are lysophospholipids. The ligand for EDG3 is sphingosine-1-phosphate. There are 8 known members of the EDG receptor family. They have been implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. The couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG3 is expressed in cardiovascular, leukocyte-containing and other tissues.

Endothelial Cell Differentiation Gene-8 (EDG-8) belongs to a family of G-protein coupled receptors whose ligands are lysophospholipids. The ligand for EDG-8 is sphingosine-1-phosphate. There are 8 known members of the EDG receptor family and they are implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival and suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. They couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG-8 is expressed in oligodendrocytes and fibrous astrocytes in the rat brain.

EDG-1 belongs to a family of G-protein coupled receptors whose ligands are lysophospholipids. The ligand for EDG-1 is sphingosine-1-phosphate. There are 8 known members of the EDG receptor family and they are implicated in mediating growth related effects such as induction of cellular proliferation, alterations in differentiation and survival and suppression of apoptosis. They also evoke cellular effector functions that are dependent on cytoskeletal responses such as contraction, secretion, adhesion and chemotaxis. EDG receptors are developmentally regulated and differ in tissue distribution. They couple to multiple types of G proteins to signal through ras and MAP kinase, rho, phospholipase C and several protein tyrosine kinases. EDG-1 is expressed in cardiovascular, leukocyte- containing and other tissues.

Sphingomyelin (SM) is a major component of animal plasma membranes. Its production involves the transfer of phosphocholine from phosphatidylcholine and then onto ceramide. This also yields diacylglycerol as a side product. The reaction is catalysed by SM synthase, an important enzyme in the regulation of diacylglycerol and ceramide as anti- and proapoptotic stimuli. SM synthesis occurs in the lumen of the Golgi as well as on or at the cell surface. It is uncertain which SM enzyme forms are present at these differnet cellular locations. Human, mouse and Caenorhabditis elegans genomes each contain at least two different SM synthase (SMS) genes. Human SMS1 is localised to the Golgi, SMS2 resides primarily at the plasma membrane.

Sphingomyelin (SM) is a major component of animal plasma membranes. Its production involves the transfer of phosphocholine from phosphatidylcholine and then onto ceramide. This also yields diacylglycerol as a side product. The reaction is catalysed by SM synthase, an important enzyme in the regulation of diacylglycerol and ceramide as anti- and proapoptotic stimuli. SM synthesis occurs in the lumen of the Golgi as well as on or at the cell surface. It is uncertain which SM enzyme forms are present at these differnet cellular locations. Human, mouse and Caenorhabditis elegans genomes each contain at least two different SM synthase (SMS) genes. Human SMS1 is localised to the Golgi, SMS2 resides primarily at the plasma membrane.

Sphingomyelin (SM) is a major component of animal plasma membranes. Its production involves the transfer of phosphocholine from phosphatidylcholine and then onto ceramide. This also yields diacylglycerol as a side product. The reaction is catalysed by SM synthase, an important enzyme in the regulation of diacylglycerol and ceramide as anti- and proapoptotic stimuli. SM synthesis occurs in the lumen of the Golgi as well as on or at the cell surface. It is uncertain which SM enzyme forms are present at these differnet cellular locations. Human, mouse and Caenorhabditis elegans genomes each contain at least two different SM synthase (SMS) genes. Human SMS1 is localised to the Golgi, SMS2 resides primarily at the plasma membrane.

A bidirectional lipid cholinephosphotransferases capable of converting phosphatidylcholine (PC) and ceramide to sphingomyelin (SM) and diacylglycerol (DAG) and the inverse reaction. Direction is dependent on the relative concentrations of DAG and ceramide as phosphocholine acceptors. Directly and specifically recognizes the choline head group on the substrate. Also requires two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. May not function strictly as a SM synthase. Inhibited by bacterial PC-phospholipase C inhibitor D609. Localized to Golgi apparatus; Golgi membrane; multi-pass membrane protein. Possibly present on Brain, heart, kidney, liver, muscle and stomach.

A bidirectional lipid cholinephosphotransferases capable of converting phosphatidylcholine (PC) and ceramide to sphingomyelin (SM) and diacylglycerol (DAG) and the inverse reaction. Direction is dependent on the relative concentrations of DAG and ceramide as phosphocholine acceptors. Directly and specifically recognizes the choline head group on the substrate. Also requires two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. May not function strictly as a SM synthase. Inhibited by bacterial PC-phospholipase C inhibitor D609. Localized to Golgi apparatus; Golgi membrane; multi-pass membrane protein. Possibly present on Brain, heart, kidney, liver, muscle and stomach.

Sphingomyelin phosphodiesterase 3 catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these two cellular events independently. It also hydrolyzes sphingosylphosphocholine. Sphingomyelin phosphodiesterase 3 regulates the cell cycle by acting as a growth suppressor in confluent cells. It likely acts as a regulator of postnatal development and participates in bone and dentin mineralization. It is activated by unsaturated fatty acids and phosphatidylserine. it is predominantly expressed in the brain.

Sphingomyelin phosphodiesterase 3 catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these two cellular events independently. It also hydrolyzes sphingosylphosphocholine. Sphingomyelin phosphodiesterase 3 regulates the cell cycle by acting as a growth suppressor in confluent cells. It likely acts as a regulator of postnatal development and participates in bone and dentin mineralization. It is activated by unsaturated fatty acids and phosphatidylserine. it is predominantly expressed in the brain.

Sphingomyelin phosphodiesterase 3 catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these two cellular events independently. It also hydrolyzes sphingosylphosphocholine. Sphingomyelin phosphodiesterase 3 regulates the cell cycle by acting as a growth suppressor in confluent cells. It likely acts as a regulator of postnatal development and participates in bone and dentin mineralization. It is activated by unsaturated fatty acids and phosphatidylserine. it is predominantly expressed in the brain.

SPARC is a key factor in cell-matrix interactions and possibly tumour aggressiveness. The SPARC gene, which encodes a multifunctional glycoprotein with roles in tissue development, remodelling and fibrosis. A regulator of cell-extracellular matrix (ECM) interactions, SPARC represents a major factor in the ECM remodelling occurring during tumour invasion. in silico analysis reveals 4 UTR-SNPs located in the 3 -UTR of the SPARC gene, corresponding to 1474 g a, 1551 g c, 1922 t g and 2072 c t changes, which are significantly associated with tumoral state of the tissue. Of all hits, the 2072 SPARC polymorphism had the best association with cancer._x000B__x000B_SPARC therefore is a gene involved in a number of diseases including rheumatoid arthritis, scleroderma, tumor development and metastasis. SPARC variants have been detected in tumour samples of patients with acute myeloblastic leukemia (AML).