S1PR1

What is S1PR1 protein?

S1PR1 (sphingosine-1-phosphate receptor 1) is a protein coding gene which situated on the short arm of chromosome 1 at locus 1p21. The protein encoded by this gene is structurally similar to G protein-coupled receptors and is highly expressed in endothelial cells. It binds the ligand sphingosine-1-phosphate with high affinity and high specificity, and suggested to be involved in the processes that regulate the differentiation of endothelial cells. Activation of this receptor induces cell-cell adhesion. The S1PR1 protein is consisted of 382 amino acids and its molecular mass is approximately 42.8 kDa.

What is the function of S1PR1 protein?

S1PR1 protein is required for normal chemotaxis toward sphingosine 1-phosphate, normal embryonic heart development, normal cardiac morphogenesis and normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. It plays an important role in the regulation of sprouting angiogenesis, vascular maturation, the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis. It could inhibit sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Also it plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury.

S1PR1 related Signaling pathways

S1PR1 is one of the five receptors for S1P. When S1P binds to S1PR1, it triggers downstream signaling events that regulate various cellular processes, including an increase in intracellular calcium levels, activation of protein kinase pathways (such as PI3K/Akt and ERK1/2), and regulation of gene expression. Meanwhile, S1P and S1PR1 signaling still plays a role in maintaining the integrity of the blood-brain barrier and T-cell migration from lymphoid organs to peripheral tissues. S1PR1 signaling is also implicated in cardiac function and protection against myocardial ischemia/reperfusion injury.

Fig6. Sphingolipid signaling regulates tight and adherens junctions through S1PRs. All S1PRs can signal via Gi, Gi activation leads to stimulation of phosphoinositide 3-kinases (PI3K) and Tiam1, which stimulate Rac1.

S1PR1 Related Diseases

Dysregulation of S1PR1 signaling has been implicated in various diseases. Some of the diseases associated with S1PR1 dysregulation include: Multiple Sclerosis (MS), Asthma, Cardiovascular diseases such as atherosclerosis, hypertension, and myocardial infarction. S1PR1 is involved in tumor growth, angiogenesis, and metastasis in various types of cancer. Altered expression or activity of S1PR1 has been linked to tumor progression and poor prognosis in several malignancies, including breast cancer, lung cancer, and colorectal cancer. Other diseases like inflammatory bowel disease (IBD) and diabetes are associated with the dysregulation of S1PR1.

Bioapplications of S1PR1

Given S1PR1 plays an important role in a variety of diseases including immunomodulation, cancer, neurological disorders and so on, drug development targeting S1PR1 has become an important therapeutic strategy. For example, Targeting S1PR1 signaling could have implications in promoting blood vessel formation in tissue engineering and regenerative medicine, as well as in treating vascular diseases such as diabetic retinopathy and atherosclerosis.