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Regulation of phospholipase D
1Howard Hughes Medical Institute and Vanderbilt University Medical Center, Nashville, TN 38232-0295, USA. john.exton@mcmail.vanderbilt.edu
FEBS Letters
|October 29, 2002
Summary
Phospholipase D (PLD) structure and function are elucidated through studies of plant, bacterial, and mammalian enzymes. Key domains and regulatory interactions reveal complex activation pathways for PLD1 and PLD2.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Background:
- The phospholipase D (PLD) superfamily includes plant, bacterial, and mammalian enzymes.
- Mammalian PLD isozymes (PLD1 and PLD2) play crucial roles in cellular signaling.
- Understanding PLD structure and regulation is essential for deciphering its biological functions.
Purpose of the Study:
- To investigate the structural basis of the catalytic mechanism in mammalian PLD isozymes.
- To identify and characterize regulatory domains and interactions of PLD1 and PLD2.
- To elucidate the pathways involved in agonist-mediated activation of PLD in vivo.
Main Methods:
- Structural studies of plant and bacterial PLD members.
- Site-directed mutagenesis and sequence comparison analyses.
- Investigation of protein-protein interactions with regulatory factors.
Main Results:
- Conserved HKD domains are critical for the catalytic center and mechanism of mammalian PLD.
- Pleckstrin homology and phox homology domains at the N-terminus and a C-terminal sequence are essential for catalysis.
- PLD1 interacts with protein kinase C and small G proteins (Rho, ADP-ribosylation factor family), influencing its activity.
Conclusions:
- Mammalian PLD1 and PLD2 possess complex regulatory mechanisms involving multiple domains and protein interactions.
- Protein kinase C and small G proteins directly regulate PLD activity through specific binding sites.
- Agonist-induced activation of PLD in vivo likely involves intricate, multi-pathway signaling cascades.