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Details for receptor: Lysophosphatidic acid receptor 2

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EndoNet ID: ENR00758

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Synonyms

  • edg4
  • LPA receptor 2
  • LPAR2
  • Lysophosphatidic acid receptor Edg-4
  • Lysophosphatidic acid receptor 2

General information

  • Belongs to the G-protein coupled receptor 1 family.
  • Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins.
  • Plays a key role in phospholipase C-beta (PLC-beta) signaling pathway. [1]
  • Stimulates phospholipase C (PLC) activity in a manner that is independent of RALA activation. [2]
  • LPA2 shows little selectivity for the number and position of double bonds in the acyl chain of their lipid ligands. [3]

Links to other resources

UniProt Q9HBW0
Ensembl ENST00000407877

Subunit information

Subunit (1 times)

Sequence 
MVIMGQCYY NETIGFFYN NSGKELSSH 
WRPKDVVVV ALGLTVSVL VLLTNLLVI 
AAIASNRRF HQPIYYLLG NLAAADLFA 
GVAYLFLMF HTGPRTARL SLEGWFLRQ 
GLLDTSLTA SVATLLAIA VERHRSVMA 
VQLHSRLPR GRVVMLIVG VWVAALGLG 
LLPAHSWHC LCALDRCSR MAPLLSRSY 
LAVWALSSL LVFLLMVAV YTRIFFYVR 
RRVQRMAEH VSCHPRYRE TTLSLVKTV 
VIILGAFVV CWTPGQVVL LLDGLGCES 
CNVLAVEKY FLLLAEANS LVNAAVYSC 
RDAEMRRTF RRLLCCACL RQSTRESVH 
YTSSAQGGA STRIMLPEN GHPLMDSTL
UniProt Q9HBW0-1

Binding hormones

  • lysophosphatidic acid
    • Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities.

Anatomical structures with this receptor

  • testis

  • peripheral blood leukocytes

  • pancreas

  • spleen

  • thymus

  • prostate

  • vascularendothelial_cell

  • hair_follicle

  • continuous_vascular_endothelial_cell_of_blood_vessels_and_lymphatics

  • ovary

    Induced phenotypes

    • Ovarian cancer
      • LPA receptor 2 is a distinctive marker of ovarian cancer cells that transduces growth-promoting signals from the high local concentrations of LPA characteristic of aggressive ovarian cancer. [4]
    • Ovarian cancer
      • LPA was shown to have potent protumorigenic effects on OCCs including cell survival, proliferation, increased migration and tissue invasion, activation of vascular endothelial growth factor, metalloproteinase, and urokinase-type plasminogen activator, and protection from cisplatin toxicity. These effects are mediated primarily by the activation of LPA2, which is known to promote proliferation, migration, and invasion of gynecological cancer cells in vitro and in vivo. [5]
      • LPA2 is upregulated in OCCs and can be activated by low nanomolar concentrations of LPA, well below the basal serum concentration. [6]

  • lymphocyte

    Induced phenotypes

    • regulation of immune response
      • LPA receptor 2 is widely expressed in the adult mouse and might be involved in the control of lymphocyte function. [3]

  • leukocyte

  • astrocyte

    Induced phenotypes

    • astrocyte differentiation
      • Astrocytes primed by LPA increase neuronal differentiation, likely through as yet unidentified soluble factors, and this activity is dependent on activation of LPA2 in astrocytes. [7]

  • Schwann_cell

    Induced phenotypes

    • myelin formation in the peripheral nervous system
      • LPA2 signaling appears to be involved in SC function, because its activation results in the upregulation of myelin P0 protein in cultured SCs. [8]
    • myelin formation in the peripheral nervous system
      • In addition to the role for myelination during developmental stages, evidence indicates a role for LPA signaling in remyelination after injuries such as neuropathic pain and nerve transection where LPA2 is upregulated despite very low levels under basal conditions. [9]
    • regulation of myelination
      • Schwann cells (SCs) are the myelinating cells of the peripheral nervous system. SCs express LPA2, and activation of this receptor is known to affect processes associated with myelination. [10]

  • T-lymphocyte

    Induced phenotypes

    • negative regulation of interleukin-2 production
      • LPA inhibits interleukin-2 (IL-2) production in unstimulated T cells that predominantly express LPA2. [11]
    • regulation of T cell chemotaxis
      • LPA enhances chemotaxis in unstimulated T cells that predominantly express LPA2. [12]

  • digestive_system

    Induced phenotypes

    • gastrointestinal cancer
      • LPA is implicated in the progression of gastrointestinal cancers. LPA stimulates proliferation, migration, and invasion primarily through the activation of LPA2. [6]

  • neuron

    Induced phenotypes

    • negative regulation of neuron projection development
      • Overexpression of LPA2 results in neurite retraction and cell rounding when stimulated with LPA. [13]

  • stomach

  • kidney

  • lung

  • fetal brain

    Induced phenotypes

    • brain development
      • LPA2 is implicated in brain formation during embryonic development. [14]

  • corpus_luteum

    Induced phenotypes

    • negative regulation of progesterone biosynthetic process
      • In luteal cells temporally coexpressing endogenous LPA2 receptor during mid-cycle, LPA inhibits agonist-stimulated progesterone production at a step distal to the cyclic AMP formation and before the steroid synthesis in mitochondria. [15]

  • smooth_muscle_cell

    Induced phenotypes

    • positive regulation of smooth muscle cell migration
      • LPA induces the proliferation and migration of vascular smooth muscle cells (VSMCs). [16]
      • LPA1 and LPA2 were found to exhibit opposing effects on primary VSMCs derived from knockout mice. The migration of SMCs was increased in Lpar1−/− mice but attenuated in Lpar1−/−/Lpar2−/− mice, thus identifying LPA1 and LPA2 as negative and positive chemotactic mediators, respectively. [17]
Reference