Pathways & interactions
G2A lysophosphatidylcholine receptor (IPR005388)
Short name: G2A_lysphc_rcpt
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- G2A lysophosphatidylcholine receptor (IPR005388)
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [PMID: 12679517]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [PMID: 8170923]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 16753280]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [PMID: 12679517]. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [PMID: 23020293].
The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [PMID: 2111655, PMID: 2830256, PMID: 8386361].
An orphan receptor, G2A, has recently been identified that acts as a high affinity receptor for lysophosphatidylcholine (LPC) and a lower affinity receptor for the related lysophospholipid, SPC [PMID: 11474113]. G2A is expressed mainly in lymphocytes and its expression is up-regulated by stress and prolonged mitogenic signals. Mice lacking the receptor have been found to develop a late-onset autoimmune disease [PMID: 11371358]. It has therefore been suggested that G2A may function as a sensor of LPC levels at sites of inflammation and act as a negative regulator of lymphocyte growth to limit expansion of tissue-infiltrating cells and overt autoimmune disease. Activation of G2A by LPC results in an increase in intracellular calcium levels (through coupling to Gi proteins) and activation of MAP kinases. The receptor has also been shown to couple to G13 proteins, causing RhoA activation and formation of actin stress fibres.
- PR01563 (G2ARECEPTOR)