Phospholipase A2

2022-02-28: reference:

Phospholipase A2 #

Removes one fatty acid from Phosphatidylcholine, producing Lysophosphatidylcholine.

• Exclusively targets sn-2, which is always(?) Arachidonic Acid.
  • Indeed, PLA1 targets the sn-1 fatty acid. However it it snot well-studied due to difficulties isolating it and so on.
• It is dependent on (micromolar) Ca2+ influx (though there is a iPLA2 (Ca2+ independent PLA).
  • Ca2+ binds to a C2 domain (which is also found on PTEN, PI3K, synaptotagmin, and some others ( wikipedia has a giant list)). The main role of C2 domains however is binding to the membrane domain - it’s just in the case of cPLA2 it’s dependent on Ca2+ binding to induce a confortmational change first.
• Dependent on Ser505 phosphorylation by primarily MAPK, but possibly other kinases:
  • Ser515 phosphorylation-independent regulation of cytosolic phospholipase A2alpha (cPLA2alpha) by calmodulin-dependent protein kinase: possible interaction with catalytic domain A of cPLA2alpha
  • Regulatory Mechanism and Physiological Role of Cytosolic Phospholipase A2
    • Phosphorylated by MAPKs on Ser505
    • CAMK II on Ser515,
    • Ser727: MAPK-interacting kinase Mnk1 or a closely related isoform
    • Phosphorylation on either Ser505, Ser515, or Ser727 increases its intrinsic enzymatic activity 2- to 3-fold in vitro.
    • Mutation of Ser505 or Ser727 results in low activity in liberating arachidonic acid from cells at submicromolar intracellular Ca2
      concentra- tions.
• Ceramide-1-phosphate activates cytosolic phospholipase A2alpha directly and by PKC pathway - Ceramide-1-phosphate at 30 microM alone induced AA release from L929 cells without an increase in intracellular Ca2+ concentration. This was decreased by a PKC inhibitor.
  • The C1P-induced increase of enzymatic activity synergized in the presence of Ca2+.