Lysophosphatidic acid (LPA) is a

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

derivative that can act as a

signaling In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' ...

molecule.

Function

LPA acts as a potent

mitogen A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a ...

due to its activation of three high-affinity

G-protein-coupled receptors G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

called

LPAR1 Lysophosphatidic acid receptor 1 also known as LPA1 is a protein that in humans is encoded by the ''LPAR1'' gene. LPA1 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). Function The integral ...

LPAR2 Lysophosphatidic acid receptor 2 also known as LPA2 is a protein that in humans is encoded by the ''LPAR2'' gene. LPA2 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). Function This gene enco ...

, and

LPAR3 Lysophosphatidic acid receptor 3 also known as LPA3 is a protein that in humans is encoded by the ''LPAR3'' gene. LPA3 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). Function This gene enc ...

(also known as EDG2, EDG4, and EDG7). Additional, newly identified LPA receptors include

LPAR4 Lysophosphatidic acid receptor 4 also known as LPA4 is a protein that in humans is encoded by the ''LPAR4'' gene. LPA4 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). See also * Lysophospholip ...

(P2RY9, GPR23),

LPAR5 Lysophosphatidic acid receptor 5 also known as LPA5 is a protein that in humans is encoded by the ''LPAR5'' gene. LPA5 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). See also * Lysophosphol ...

(GPR92) and

LPAR6 Lysophosphatidic acid receptor 6, also known as LPA6, P2RY5 and GPR87, is a protein that in humans is encoded by the ''LPAR6'' gene. LPA6 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). The p ...

(P2RY5, GPR87).

Clinical significance

Because of its ability to stimulate

cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation re ...

, aberrant LPA-signaling has been linked to cancer in numerous ways. Dysregulation of

autotaxin Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (E-NPP 2), is an enzyme that in humans is encoded by the ''ENPP2'' gene. Function Autotaxin (ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or EN ...

or the LPA receptors can lead to hyperproliferation, which may contribute to oncogenesis and

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

. 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 Rho (uppercase Ρ, lowercase ρ or ; el, ρο or el, ρω, label=none) is the 17th letter of the Greek alphabet. In the system of Greek numerals it has a value of 100. It is derived from Phoenician letter res . Its uppercase form uses the sa ...

can be activated, subsequently activating Rho kinase. This can lead to the formation of

stress fiber Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin II (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated ...

s and cell migration through the inhibition of

myosin light-chain phosphatase Myosin light-chain phosphatase, also called myosin phosphatase (EC 3.1.3.53; systematic name yosin-light-chainphosphate phosphohydrolase), is an enzyme (specifically a serine/threonine-specific protein phosphatase) that dephosphorylates the reg ...

Metabolism

There are a number of potential routes to its biosynthesis, but the most well-characterized is by the action of a lyso phospholipase D called

, which removes the

choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but re ...

group from

lysophosphatidylcholine Lysophosphatidylcholines (LPC, lysoPC), also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholines. Overview Lysophosphatidylcholines are produced within cells mainly by the enzyme phospholipase ...

. Lysophosphatidic acid is also an intermediate in the synthesis of

phosphatidic acid Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty ac ...

Function

Clinical significance

GTPase activation

Metabolism

See also

References

Further reading