Lysophosphatidic acid

Lysophosphatidic acid
IUPAC name (2-hydroxy-3-phosphonooxypropyl) (Z)-octadec-9-enoate
Other names LPA
Identifiers
CAS number	22002-87-5 Y
PubChem	5497152
	MeSH	lysophosphatidic+acid
Jmol-3D images	Image 1
SMILES CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(=O)(O)O)O
Properties
Molecular formula	C21H41O7P
Molar mass	436.52 g/mol
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
Infobox references

Lysophosphatidic acid (LPA) is a phospholipid derivative that can act as a signaling molecule.^[1]

Function

LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3 (also known as EDG2, EDG4, and EDG7). Additional, newly identified LPA receptors include LPA4 (p2y9/GPR23), LPA5 (GPR92) and LPA6 (GPR87).

Clinical significance

Because of its ability to stimulate cell proliferation, aberrant LPA-signaling has been linked to cancer in numerous ways. Dysregulation of autotaxin or the LPA receptors can lead to hyperproliferation, which may contribute to oncogenesis and metastasis.

LPA may be the cause of pruritus (itching) in individuals with cholestatic (impaired bile flow) diseases.

GTPase activation

Downstream of LPA receptor activation, the small GTPase Rho can be activated, subsequently activating Rho kinase. This can lead to the formation of stress fibers and cell migration through the inhibition of myosin light-chain phosphatase.

Metabolism

There are a number of potential routes to its biosynthesis, but the most well-characterized is by the action of a lysophospholipase D called autotaxin, which removes the choline group from lysophosphatidylcholine.

Lysophosphatidic acid is also an intermediate in the synthesis of phosphatidic acid.

See also

• Autotaxin
• GPR35
• phosphatidic acid
• Lysophospholipid receptor

References

Further reading

• Kremer, Andreas E.; Martens, Job J.W.W.; Kulik, Wim; Ruëff, Franziska; Kuiper, Edith M.M.; Van Buuren, Henk R.; Van Erpecum, Karel J.; Kondrackiene, Jurate et al. (2010). "Lysophosphatidic Acid is a Potential Mediator of Cholestatic Pruritus". Gastroenterology 139 (3): 1008–18, 1018.e1. doi:10.1053/j.gastro.2010.05.009. PMID 20546739.  |displayauthors= suggested (help)
• Moolenaar, Wouter H. (1995). "Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger". The Journal of Biological Chemistry 270 (22): 12949–52. doi:10.1074/jbc.270.22.12949 (inactive October 28, 2012). PMID 7768880. 
• Mills, Gordon B.; Moolenaar, Wouter H. (2003). "The emerging role of lysophosphatidic acid in cancer". Nature Reviews Cancer 3 (8): 582–91. doi:10.1038/nrc1143. PMID 12894246. 
• Panupinthu, N; Lee, H Y; Mills, G B (2010). "Lysophosphatidic acid production and action: Critical new players in breast cancer initiation and progression". British Journal of Cancer 102 (6): 941–6. doi:10.1038/sj.bjc.6605588. PMC 2844037. PMID 20234370. 
• Park, S Y; Jeong, K J; Panupinthu, N; Yu, S; Lee, J; Han, J W; Kim, J M; Lee, J-S et al. (2010). "Lysophosphatidic acid augments human hepatocellular carcinoma cell invasion through LPA1 receptor and MMP-9 expression". Oncogene 30 (11): 1351–9. doi:10.1038/onc.2010.517. PMID 21102517.  |displayauthors= suggested (help)