GPR132
| GPR132 | |||
|---|---|---|---|
| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 14: 105.05 – 105.07 Mb | Chr 12: 112.81 – 112.83 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
G protein coupled receptor 132, also termed G2A, is classified as a member of the proton sensing G protein coupled receptor (GPR) subfamily. Like other members of this subfamily, i.e.
polyunsaturated fatty acid, linoleic acid
.
The G2A gene
G2A in humans is encoded by the GPR132
The mouse G2A receptor, encoded by Gpr132, has 67% amino acid identity to human G2A but does not sense pH and does not respond to certain presumptive ligands (i.e. linoleic acid metabolites) that activate the human G2A.[8]
G2A deficiency in mice
Targeted disruption of G2A in mice causes the development of a late onset (> 1 year) slowly progressive wasting and
acute myelocytic leukemia; furthermore, the forced expression of BCR-ABL in cultured rodent cells induces the expression of G2A and the overexpression of G2A inhibits the malignant growth to these cells.[11]
Thus, the G2A deficiency studies suggest that G2A functions in mice to suppress certain immune dysfunctions and BCR-ABL-related leukemic cell growth.
G2A function
pH sensor
G2A was initially defined as one of the gene products whose production was stimulated in mouse pre-B lymphocytes (see
neurons, small diameter neurons responsible for nociception, and other nerve tissues responsible for sensing pain; it is suggested that G2A in these nerve tissues detects the acid changes that occur in the extracellular media of injured tissues and signal for the perception of pain[13][9]
However, the activity of the human G2A receptor and its mouse homolog are significantly less sensitive to pH fluctuations than other pH sensing GPCRs; indeed, in studies of
thymocytes and splenocytes taken from mice deficient in either the G2A or another pH-sensing GPCR, TDAG8, TDAG8 was found critical while G2A was found dispensable for sensing pH changes.[14]
Thus, the cited functions of G2A presumed due to its pH sensing ability could reflect other means for this receptor's activation.
Receptor for lyso-phospholipids
A report working with human
neutrophils proposed that G2A was a receptor for a phospholipid, lysophosphatidylcholine (LPC), and a Sphingomyelin, sphingosylphosphorylcholine.[15] However, these studies did not give evidence that these lyso-phospholipids actually bound to G2A; some 4 years later this report was withdrawn.[16] Nonetheless, many of LPC's activities do depend on G2A; more recent data suggest that rather than acting directly as a ligand that binds to G2A, LPC alters G2A's distribution within the cell by increasing its movement from the cell interior to the cell surface and/or by preventing its movement away from the cell surface to the cell interior. That is, in neutrophils and other cell types which have internal stores of G2A in membrane-bound secretory vesicles, G2A-containing vesicles continuously merge with and move back out of a cell's surface membrane.[17] Lyso-phospholipids may act as a)) detergents to increase a cell's permeability thereby allowing entry of small extracellular molecules such as ionic calcium which trigger the movement of the intracellular vesicles to the surface membrane or b) agents that intercalate or wedge into the cell's surface membrane to promote this vesicle movement or slow this vesicle movement out of the membrane .[17][18] Such effects increase the expression of G2A at the cell surface membrane which, if G2A has a sub-stimulatory level of activity when normally express but stimulatory when it is overexpressed at the surface membrane, may lead to G2A-dependent cellular responses. With respect to this view, small decreases in extracellular pH reduce the internalization of G2A thereby increasing its surface membrane expression.[17]
LPCs that contain the unsaturated fatty acids
innate immune responses
in mice and may also do so in humans.
Receptor for fatty acid metabolites
The
UV light.[8]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000183484 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021298 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 24381558.
- ^ PMID 12086852.
- ^ "Entrez Gene: GPR132 G protein-coupled receptor 132".
- ^ PMID 19063986.
- ^ PMID 23917207.
- ^ PMID 11371358.
- ^ PMID 9770487.
- PMID 15280385.
- S2CID 38351962.>
- PMID 15665078.
- PMID 16498716|...|intentional=yes}}.)
- PMID 16498716.
- ^ PMID 24891524.
- ^ PMID 17475884.
- S2CID 32242606.
- ^ PMID 25251539.
- PMID 21297111.
- PMID 23293064.
- S2CID 220842161.
Further reading
- Bolick DT, Skaflen MD, Johnson LE, Kwon SC, Howatt D, Daugherty A, Ravichandran KS, Hedrick CC (February 2009). "G2A deficiency in mice promotes macrophage activation and atherosclerosis". Circulation Research. 104 (3): 318–27. PMID 19106413.
- Rikitake Y, Hirata K, Yamashita T, Iwai K, Kobayashi S, Itoh H, Ozaki M, Ejiri J, Shiomi M, Inoue N, Kawashima S, Yokoyama M (December 2002). "Expression of G2A, a receptor for lysophosphatidylcholine, by macrophages in murine, rabbit, and human atherosclerotic plaques". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (12): 2049–53. PMID 12482833.
- Lin P, Ye RD (April 2003). "The lysophospholipid receptor G2A activates a specific combination of G proteins and promotes apoptosis". The Journal of Biological Chemistry. 278 (16): 14379–86. PMID 12586833.
- Lum H, Qiao J, Walter RJ, Huang F, Subbaiah PV, Kim KS, Holian O (October 2003). "Inflammatory stress increases receptor for lysophosphatidylcholine in human microvascular endothelial cells". American Journal of Physiology. Heart and Circulatory Physiology. 285 (4): H1786-9. PMID 12805023.
- Witte ON, Kabarowski JH, Xu Y, Le LQ, Zhu K (January 2005). "Retraction". Science. 307 (5707): 206. PMID 15653487.
- Obinata H, Hattori T, Nakane S, Tatei K, Izumi T (December 2005). "Identification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G protein-coupled receptor G2A". The Journal of Biological Chemistry. 280 (49): 40676–83. PMID 16236715.