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.[5]
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.
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