Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0344329 (
collapse
)
28,634
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Bradykinin (BK) activates
phospholipase D
(PLD) and induces several responses such as catecholamine secretion,
collapse
of growth cones, and gene expression in PC12 pheochromocytoma cells. Although two distinct PLD isozymes, PLD1 and PLD2, have been cloned from mammalian cells, the regulatory mechanism for each PLD isozyme by BK is not clear. In our present study, we investigated the activation mechanism of PLD2 by BK in PLD2-overexpressing PC12 cells. BK stimulated PLD2 activity in a concentration-dependent manner within 1 min and this activation was inhibited by pretreatment of the cells with protein kinase C (PKC) inhibitor. PKCalpha and PKCdelta translocated from cytosol to membrane upon BK treatment, and rottlerin potently inhibited the activation of PLD2 by BK. These results suggest that BK activates PLD2 via PKCdelta in PC12 cells.
...
PMID:Bradykinin activates phospholipase D2 via protein kinase cdelta in PC12 cells. 1105 4
Phosphatidylcholine (PC)-specific
phospholipase D
(PLD) hydrolyzes the phosphodiester bond of the PC to generate phosphatidic acid (PA) and regulates several subcellular functions. Mammalian genomes contain two genes encoding distinct isoforms of PLD in contrast with invertebrate genomes that include a single PLD gene. However, the significance of two genes within a genome encoding the same biochemical activity remains unclear. Recently, loss of function in the only PLD gene in
Drosophila
was reported to result in reduced PA levels and a PA-dependent
collapse
of the photoreceptor plasma membrane due to defects in vesicular transport. Phylogenetic analysis reveals that human PLD1 (hPLD1) is evolutionarily closer to dPLD than human PLD2 (hPLD2). In the present study, we expressed hPLD1 and hPLD2 in
Drosophila
and found that while reconstitution of hPLD1 is able to completely rescue retinal degeneration in a loss of function dPLD mutant, hPLD2 was less effective in its ability to mediate a rescue. Using a newly developed analytical method, we determined the acyl chain composition of PA species produced by each enzyme. While dPLD was able to restore the levels of most PA species in
dPLD
3.1
cells, hPLD1 and hPLD2 each were unable to restore the levels of a subset of unique species of PA. Finally, we found that in contrast with hPLD2, dPLD and hPLD1 are uniquely distributed to the subplasma membrane region in photoreceptors. In summary, hPLD1 likely represents the ancestral PLD in mammalian genomes while hPLD2 represents neofunctionalization to generate PA at distinct subcellular membranes.
...
PMID:Functional analysis of mammalian phospholipase D enzymes. 3118 47
