Lysophosphatidic acid

Function

LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPAR1, LPAR2, and LPAR3 (also known as EDG2, EDG4, and EDG7). Additional, newly identified LPA receptors include LPAR4 (P2RY9, GPR23), LPAR5 (GPR92) and LPAR6 (P2RY5, 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 cause 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 by inhibiting myosin light-chain phosphatase.

Metabolism

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

Lysophosphatidic acids are also intermediates in the synthesis of phosphatidic acids.

References

References

1. (1989-10-06). "Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins". Cell.
2. (2015-09-05). "Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma". Molecular and Cellular Endocrinology.
3. Moolenaar, Wouter H.. (1995-06-02). "Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger ∗". Journal of Biological Chemistry.
4. (2003-11-01). "Molecular mechanisms of lysophosphatidic acid action". Progress in Lipid Research.
5. (2014). "Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions". FEBS Letters.