Mastoparan selectively activates phospholipase D2 in cell membranes
Ahmed Chahdi1, Wahn Soo Choi, Young Mi Kim
1Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1760, USA.
The Journal of Biological Chemistry
|January 31, 2003
Summary
Mastoparan activates phospholipase D2 (PLD2) in mast cells, independent of common signaling pathways. This finding provides a new tool for studying PLD2 regulation and its interactions with other proteins.
Area of Science:
- Biochemistry
- Cell Biology
- Signal Transduction
Background:
- Phospholipase D (PLD) isoforms PLD1 and PLD2 require phosphatidylinositol 4,5-bisphosphate for activity.
- PLD2 activation is intrinsic, while PLD1 requires additional factors like ADP-ribosylation factor-1 (ARF-1) and protein kinase Calpha.
Purpose of the Study:
- To investigate the effect of mastoparan on PLD activity in rat basophilic leukemia 2H3 mast cells.
- To determine which PLD isoform is activated by mastoparan and the underlying regulatory mechanisms.
Main Methods:
- Utilized membrane fractions from rat basophilic leukemia 2H3 mast cells.
- Employed mastoparan, pertussis toxin, and other agents to study PLD activity.
- Performed overexpression studies of PLD1 and PLD2.
- Conducted kinetic studies with phosphatidylinositol 4,5-bisphosphate and oleate.
Main Results:
- Mastoparan stimulates intrinsic PLD activity, primarily PLD2, in plasma membrane-enriched fractions.
- Overexpression of PLD2, not PLD1, significantly increased mastoparan-inducible PLD activity.
- Mastoparan stimulates PLD2 independently of G(i), ARF-1, protein kinase C, and calcium.
- Mastoparan acts synergistically with phosphatidylinositol 4,5-bisphosphate and is competitively inhibited by oleate.
Conclusions:
- Mastoparan is a valuable tool for investigating the regulation of PLD2.
- Mastoparan's activation of PLD2 is independent of canonical signaling pathways.
- Further studies can explore mastoparan's interactions with other signaling proteins to elucidate PLD2 function.
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