Phospholipase D

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phospholipase D1, phosphatidylcholine-specific
Identifiers
Symbol PLD1
Entrez 5337
HUGO 9067
OMIM 602382
RefSeq NM_002662
UniProt Q13393
Other data
Locus Chr. 3 q26
phospholipase D2
Identifiers
Symbol PLD2
Entrez 5338
HUGO 9068
OMIM 602384
RefSeq NM_002663
UniProt O14939
Other data
Locus Chr. 17 p13.3

There are two isoforms of Phospholipase D in the mammalian cell PLD1 and PLD2. PLD (EC 3.1.4.4), is located in the plasma membrane and catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid (PA), releasing the soluble choline headgroup into the cytosol:

As choline is very abundant in the cell, PLD activity does not significantly affect choline levels, and choline is unlikely to play any role in signalling.

Phosphatidic acid is a signal molecule and acts to recruit SK1 to membranes. PA is extremely short lived and is rapidly hydrolised by the enzyme PA phosphohydrolase to form diacylglycerol (DAG). DAG may also be converted to PA by DAG kinase. Although PA and DAG are interconvertible, they do not act in the same pathways. Stimuli that activate PLD do not activate enzymes downstream of DAG and vice versa.

It is possible that, though PA and DAG are interconvertible, separate pools of signalling and non-signalling lipids may be maintained. Studies have suggested that DAG signalling is mediated by polyunsaturated DAG while PLD derived PA is monounsaturated or saturated. Thus functional saturated/monounsaturated PA can be degraded by hydrolysing it to form non-functional saturated/monounsaturated DAG while functional polyunsaturated DAG can be degraded by converting it into non-functional polyunsaturated PA.[1][2][3]

Finally, a lysophospholipase D called autotaxin was recently identified as having an important role in cell-proliferation through its product, lysophosphatidic acid (LPA).

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[edit] References

  1. ^ Bocckino S, Blackmore P, Wilson P, Exton J (1987). "Phosphatidate accumulation in hormone-treated hepatocytes via a phospholipase D mechanism". J Biol Chem 262 (31): 15309–15. PMID 3117799. 
  2. ^ Bocckino S, Wilson P, Exton J (1987). "Ca2+-mobilizing hormones elicit phosphatidylethanol accumulation via phospholipase D activation". FEBS Lett 225 (1-2): 201–4. doi:10.1016/0014-5793(87)81157-2. PMID 3319693. 
  3. ^ Hodgkin M, Pettitt T, Martin A, Michell R, Pemberton A, Wakelam M (1998). "Diacylglycerols and phosphatidates: which molecular species are intracellular messengers?". Trends Biochem Sci 23 (6): 200–4. doi:10.1016/S0968-0004(98)01200-6. PMID 9644971. 

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