Mechanism of cAMP-induced Ca2+ influx in Dictyostelium: role of phospholipase A2

Biochem J. 1997 Oct 1;327 ( Pt 1)(Pt 1):233-8. doi: 10.1042/bj3270233.

Abstract

cAMP-induced Ca2+ influx in Dictyostelium follows two pathways: a G-protein-dependent pathway where influx is reduced by 50-70% in Galpha2 and Gbeta-negative strains and a heterotrimeric G-protein-independent pathway. Using a pharmacological approach, we found that phospholipase A2 (PLA2) is the target of both pathways. The products of PLA2 activity, arachidonic acid (AA) and palmitic acid, induced Ca2+ influx to a similar extent as cAMP. Half-maximal activation occurred at 3 microM AA and saturation at 10 microM AA. The response to AA was quantitatively similar throughout early differentiation and thus independent of cAMP-receptor concentration. Synergy experiments revealed that cAMP and AA acted through identical pathways. The PLA2-activating peptide, a peptide with sequence similarity to the G-protein beta-subunit, activated Ca2+ influx. The G-protein-independent pathway was sensitive to genistein but not to blockers of protein kinase C and other kinases, suggesting that tyrosine kinase may directly or indirectly activate PLA2 in this case.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / pharmacology
  • Calcium / metabolism*
  • Cyclic AMP / pharmacology*
  • Dictyostelium / metabolism*
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Proteins / metabolism
  • Genistein / pharmacology
  • Ion Transport
  • Lipoprotein Lipase / antagonists & inhibitors
  • Palmitic Acid / pharmacology
  • Phospholipases A / antagonists & inhibitors
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Protein Kinase C / antagonists & inhibitors
  • Proteins / pharmacology
  • Signal Transduction / physiology

Substances

  • Enzyme Inhibitors
  • Proteins
  • phospholipase A2-activating protein
  • Arachidonic Acid
  • Palmitic Acid
  • Genistein
  • Cyclic AMP
  • Protein Kinase C
  • Phospholipases A
  • Lipoprotein Lipase
  • Phospholipases A2
  • GTP-Binding Proteins
  • Calcium