Phospholipase D: Difference between revisions
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'''Phospholipase D''' ({{EC number|3.1.4.4}}, ''lipophosphodiesterase II'', ''lecithinase D'', ''choline phosphatase'') ''' |
'''Phospholipase D''' ({{EC number|3.1.4.4}}, ''lipophosphodiesterase II'', ''lecithinase D'', ''choline phosphatase'') ('''PLD''') is an [[enzyme]] of the [[phospholipase]] [[protein superfamily|superfamily]]. Phospholipases are widely occurring, and can be found in myriad [[organism|organisms]], including [[bacteria]], [[yeast]], [[plants]], [[animals]], even [[virus|viruses]].<ref name="pmid16143829">{{cite journal | author = Jenkins GM, Frohman MA | title = Phospholipase D: a lipid centric review. | journal = Cell Mol Life Sci. | volume = 62 | issue = 19-20 | pages = 2305–16 |date=October 2005 | pmid = 16143829 | doi = 10.1007/s00018-005-5195-z| url = | issn = }}</ref><ref name="pmid11987824 ">{{cite journal | author = Exton JH| title = Phospholipase D-structure, regulation and function. | journal = Rev Physiol Biochem Pharmacol. | volume = 1 | issue = 144 | pages = 1-94 |date=2002 | pmid = 11987824 | doi = 10.2174/157436206778226941 | url = | issn = }}</ref> Phospholipase D’s principal [[Enzyme substrate|substrate]] is [[phosphatidylcholine]], which it [[hydrolysis|hydrolyzes]] to produce the [[Cell signaling|signal]] [[molecule]] [[phosphatidate|phosphatidic acid]] (PA), and [[soluble]] [[choline]]. [[Plants]] contain numerous [[genes]] that encode various PLD [[isoenzyme|isoenzymes]], with [[molecular mass|molecular weights]] ranging from 90-125 [[atomic mass unit|kDA]].<ref name="pmid22339628 ">{{cite journal | author = Kolesnikov YS, Nokhrina KP, Kretynin SV, Volotovski ID, Martinec J, Romanov GA, Kravets VS. | title = Molecular structure of phospholipase D and regulatory mechanisms of its activity in plant and animal cells. | journal = Biochemistry (Mosc). | volume = 77 | issue = 1 | pages = 1-14 |date=January 2012 | pmid = 22339628 | doi = 10.1134/S0006297912010014| url = | issn = }}</ref> [[Mammals|Mammalian]] [[cells]] encode two isoforms of phospholipase D: [[PLD1]] and [[PLD2]].<ref name="pmid21447092">{{cite journal | author = Peng X., M. A. Frohman | title = Mammalian Phospholipase D Physiological and Pathological Roles. | journal = Acta Physiologica | volume = 204 | issue = 2 | pages = 219–226 |date=February 2012 | pmid = 21447092 | doi = 10.1111/j.1748-1716.2011.02298.x | url = | issn = }}</ref> Phospholipase D is an important player in many [[physiology|physiological]] processes, including [[membrane trafficking]], [[cytoskeleton|cytoskeletal]] reorganization, [[receptor-mediated endocytosis]], [[exocytosis]], and [[cell migration]].<ref name="pmid14517341 ">{{cite journal | author = Foster DA | title = Phospholipase D in cell proliferation and cancer. | journal = Mol Cancer Res. | volume = 1 | issue = 11 | pages = 789-800 |date=September 2003 | pmid = 14517341 | doi = 10.2174/157436206778226941 | url = | issn = }}</ref> Through these processes, it has been further implicated in the [[pathophysiology]] of multiple [[disease|diseases]]: in particular the progression of [[Parkinson's disease|Parkinson’s]] and [[Alzheimer's disease|Alzheimer’s]], as well as various [[cancer|cancers]].<ref name="pmid22339628 ">{{cite journal | author = Kolesnikov YS, Nokhrina KP, Kretynin SV, Volotovski ID, Martinec J, Romanov GA, Kravets VS. | title = Molecular structure of phospholipase D and regulatory mechanisms of its activity in plant and animal cells. | journal = Biochemistry (Mosc). | volume = 77 | issue = 1 | pages = 1-14 |date=January 2012 | pmid = 22339628 | doi = 10.1134/S0006297912010014| url = | issn = }}</ref><ref name="pmid14517341 ">{{cite journal | author = Foster DA | title = Phospholipase D in cell proliferation and cancer. | journal = Mol Cancer Res. | volume = 1 | issue = 11 | pages = 789-800 |date=September 2003 | pmid = 14517341 | doi = 10.2174/157436206778226941 | url = | issn = }}</ref> |
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== Function == |
== Function == |
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Revision as of 05:33, 3 March 2014
| phospholipase D | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 3.1.4.4 | ||||||||
| CAS no. | 9001-87-0 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
Phospholipase D (EC 3.1.4.4, lipophosphodiesterase II, lecithinase D, choline phosphatase) (PLD) is an enzyme of the phospholipase superfamily. Phospholipases are widely occurring, and can be found in myriad organisms, including bacteria, yeast, plants, animals, even viruses.[1][2] Phospholipase D’s principal substrate is phosphatidylcholine, which it hydrolyzes to produce the signal molecule phosphatidic acid (PA), and soluble choline. Plants contain numerous genes that encode various PLD isoenzymes, with molecular weights ranging from 90-125 kDA.[3] Mammalian cells encode two isoforms of phospholipase D: PLD1 and PLD2.[4] Phospholipase D is an important player in many physiological processes, including membrane trafficking, cytoskeletal reorganization, receptor-mediated endocytosis, exocytosis, and cell migration.[5] Through these processes, it has been further implicated in the pathophysiology of multiple diseases: in particular the progression of Parkinson’s and Alzheimer’s, as well as various cancers.[3][5]
Function
Mammalian PLD directly interacts with kinases like PKC, ERK, TYK and controls the signalling indicating that PLD is activated by these kinases.[6] 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 hydrolysed 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.[7][8][9]
A lysophospholipase D called autotaxin was recently identified as having an important role in cell-proliferation through its product, lysophosphatidic acid (LPA).
Phospholipase D3 (PLD3), a non-classical and poorly characterized member of the PLD superfamily, has been associated with the risk of developing Alzheimer's disease.[10]
Isoforms
Human proteins possessing phospholipase D activity include:
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Active site motif
| Phospholipase D Active site motif | |||||||||||
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| Identifiers | |||||||||||
| Symbol | PLDc | ||||||||||
| Pfam | PF00614 | ||||||||||
| InterPro | IPR001736 | ||||||||||
| SMART | SM00155 | ||||||||||
| PROSITE | PDOC50035 | ||||||||||
| SCOP2 | 1byr / SCOPe / SUPFAM | ||||||||||
| CDD | cd00138 | ||||||||||
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Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolyzing PLD is a homologue of cardiolipin synthase,[11][12] phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, and/or asparagine residues which may contribute to the active site aspartic acid. An Escherichia coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs.[13][14][15][16]
Human proteins containing this motif include:
Gallery
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Phospholipase Cleavage Sites.
References
- ^ Jenkins GM, Frohman MA (October 2005). "Phospholipase D: a lipid centric review". Cell Mol Life Sci. 62 (19–20): 2305–16. doi:10.1007/s00018-005-5195-z. PMID 16143829.
- ^ Exton JH (2002). "Phospholipase D-structure, regulation and function". Rev Physiol Biochem Pharmacol. 1 (144): 1–94. doi:10.2174/157436206778226941. PMID 11987824.
- ^ a b Kolesnikov YS, Nokhrina KP, Kretynin SV, Volotovski ID, Martinec J, Romanov GA, Kravets VS. (January 2012). "Molecular structure of phospholipase D and regulatory mechanisms of its activity in plant and animal cells". Biochemistry (Mosc). 77 (1): 1–14. doi:10.1134/S0006297912010014. PMID 22339628.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Peng X., M. A. Frohman (February 2012). "Mammalian Phospholipase D Physiological and Pathological Roles". Acta Physiologica. 204 (2): 219–226. doi:10.1111/j.1748-1716.2011.02298.x. PMID 21447092.
- ^ a b Foster DA (September 2003). "Phospholipase D in cell proliferation and cancer". Mol Cancer Res. 1 (11): 789–800. doi:10.2174/157436206778226941. PMID 14517341.
- ^ Paruch S, El-Benna J, Djerdjouri B, Marullo S, Périanin A (January 2006). "A role of p44/42 mitogen-activated protein kinases in formyl-peptide receptor-mediated phospholipase D activity and oxidant production". FASEB J. 20 (1): 142–4. doi:10.1096/fj.05-3881fje. PMID 16253958.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Cruchaga; et al. (2013). "Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease". Nature.
{{cite journal}}: Explicit use of et al. in:|author=(help) - ^ M. Nowicki and M. Frentzen (2005). "Cardiolipin synthase of Arabidopsis thaliana". FEBS Letters. 579 (10): 2161–2165. doi:10.1016/j.febslet.2005.03.007. PMID 15811335.
- ^ M. Nowicki (2006). "Characterization of the Cardiolipin Synthase from Arabidopsis thaliana". Ph.D. thesis, RWTH-Aachen University.
- ^ Ponting CP, Kerr ID (1996). "A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues". Protein Sci. 5 (5): 914–922. doi:10.1002/pro.5560050513. PMC 2143407. PMID 8732763.
- ^ Koonin EV (1996). "A duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins". Trends Biochem. Sci. 21 (7): 242–243. PMID 8755242.
- ^ Wang X, Xu L, Zheng L (1994). "Cloning and expression of phosphatidylcholine-hydrolyzing phospholipase D from Ricinus communis L". J. Biol. Chem. 269 (32): 20312–20317. PMID 8051126.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Singer WD, Brown HA, Sternweis PC (1997). "Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D". Annu. Rev. Biochem. 66: 475–509. doi:10.1146/annurev.biochem.66.1.475. PMID 9242915.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
- Phospholipase+D at the U.S. National Library of Medicine Medical Subject Headings (MeSH)