KEGG   PATHWAY: dnm04072
Entry
dnm04072                    Pathway                                
Name
Phospholipase D signaling pathway - Dasypus novemcinctus (nine-banded armadillo)
Description
Phospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). The PLD-produced PA activates signaling proteins and acts as a node within the membrane to which signaling proteins translocate. Several signaling proteins, including Raf-1 and mTOR, directly bind PA to mediate translocation or activation, respectively.
Class
Environmental Information Processing; Signal transduction
Pathway map
dnm04072  Phospholipase D signaling pathway
dnm04072

Organism
Dasypus novemcinctus (nine-banded armadillo) [GN:dnm]
Gene
101410637  DGKA; diacylglycerol kinase alpha isoform X1 [KO:K00901] [EC:2.7.1.107]
101411498  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
101411552  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
101411559  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101411563  [KO:K08732]
101411573  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101411689  [KO:K08732]
101411746  DGKZ; diacylglycerol kinase zeta isoform X3 [KO:K00901] [EC:2.7.1.107]
101412233  KRAS; GTPase KRas isoform X4 [KO:K07827]
101412328  RALGDS; ral guanine nucleotide dissociation stimulator isoform X1 [KO:K08732]
101413067  KITLG; kit ligand isoform X1 [KO:K05461]
101413281  TSC2; tuberin [KO:K07207]
101413433  [KO:K08732]
101413434  RHOA; transforming protein RhoA [KO:K04513]
101413494  [KO:K08732]
101413654  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
101413986  [KO:K16342] [EC:3.1.1.4]
101414233  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101414240  [KO:K07828]
101414344  [KO:K08732]
101414417  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
101414963  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
101415497  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
101415773  CYTH2; cytohesin-2 [KO:K18441]
101416053  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
101416386  DGKG; diacylglycerol kinase gamma isoform X2 [KO:K00901] [EC:2.7.1.107]
101416463  DNM2; dynamin-2 [KO:K23484]
101416511  [KO:K08732]
101417169  [KO:K07937]
101417345  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101417480  SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448]
101417819  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
101417880  [KO:K08090]
101417998  RHEB; GTP-binding protein Rheb [KO:K07208]
101418699  [KO:K08732]
101418748  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
101419022  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101419028  [KO:K08732]
101419332  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101419480  HRAS; GTPase HRas isoform X1 [KO:K02833]
101419675  [KO:K08732]
101419801  [KO:K08732]
101419878  PLCB4; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
101419900  [KO:K08732]
101420195  [KO:K07835]
101420315  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101420394  [KO:K08732]
101420455  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
101420546  [KO:K04369] [EC:2.7.12.2]
101420795  F2; prothrombin [KO:K01313] [EC:3.4.21.5]
101420804  LPAR1; lysophosphatidic acid receptor 1 isoform X1 [KO:K04289]
101420980  PIP5K1C; LOW QUALITY PROTEIN: phosphatidylinositol 4-phosphate 5-kinase type-1 gamma [KO:K00889] [EC:2.7.1.68]
101421064  AGT; angiotensinogen [KO:K09821]
101421211  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101421521  CYTH3; cytohesin-3 isoform X1 [KO:K18441]
101421543  [KO:K08732]
101421734  LPAR5; lysophosphatidic acid receptor 5 [KO:K08390]
101421938  [KO:K08732]
101422156  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101422441  AGPAT3; LOW QUALITY PROTEIN: 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma [KO:K13523] [EC:2.3.1.51 2.3.1.-]
101422617  SHC4; SHC-transforming protein 4 [KO:K17449]
101422732  [KO:K08048] [EC:4.6.1.1]
101423469  [KO:K06856]
101423539  [KO:K08732]
101423744  [KO:K02649]
101424126  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
101424175  [KO:K08732]
101424413  GRM8; LOW QUALITY PROTEIN: metabotropic glutamate receptor 8 [KO:K04610]
101424874  RRAS; ras-related protein R-Ras [KO:K07829]
101424964  [KO:K08732]
101425018  [KO:K08732]
101425147  [KO:K08732]
101425172  [KO:K01528] [EC:3.6.5.5]
101425228  [KO:K08732]
101425321  [KO:K00889] [EC:2.7.1.68]
101425884  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
101426738  [KO:K05242]
101426945  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101427074  AVPR1B; vasopressin V1b receptor [KO:K04227]
101427179  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858] [EC:3.1.4.11]
101427287  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
101427811  AGPAT1; 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha isoform X2 [KO:K13509] [EC:2.3.1.51]
101427927  ADCY7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
101428018  DGKB; LOW QUALITY PROTEIN: diacylglycerol kinase beta [KO:K00901] [EC:2.7.1.107]
101428037  [KO:K08732]
101428152  [KO:K04632]
101428297  PDGFRA; LOW QUALITY PROTEIN: platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
101428386  PLCG2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101428799  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101429047  [KO:K04291]
101429523  [KO:K08732]
101429652  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
101429662  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
101430180  MRAS; ras-related protein M-Ras [KO:K07831]
101430245  GRM3; metabotropic glutamate receptor 3 isoform X1 [KO:K04606]
101430570  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101430817  NRAS; GTPase NRas [KO:K07828]
101430859  [KO:K08732]
101430983  PLA2G4D; LOW QUALITY PROTEIN: cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
101431083  PLPP3; phospholipid phosphatase 3 isoform X1 [KO:K01080] [EC:3.1.3.4]
101431151  F2R; proteinase-activated receptor 1 [KO:K03914]
101431216  [KO:K04228]
101431339  [KO:K05242]
101431430  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
101431937  GRM7; metabotropic glutamate receptor 7 [KO:K04609]
101431970  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
101432225  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha isoform X1 [KO:K08089]
101432231  DGKH; diacylglycerol kinase eta isoform X4 [KO:K00901] [EC:2.7.1.107]
101432523  AGPAT5; 1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon [KO:K19007] [EC:2.3.1.51]
101432656  DNM1; dynamin-1 [KO:K01528] [EC:3.6.5.5]
101432719  [KO:K08732]
101432932  [KO:K08732]
101433245  ARF6; ADP-ribosylation factor 6 [KO:K07941]
101433347  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101433374  [KO:K08732]
101433544  SOS2; son of sevenless homolog 2 [KO:K03099]
101434069  MTOR; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101435063  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X2 [KO:K07293] [EC:3.1.3.48]
101435268  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
101435351  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101435742  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101435973  [KO:K08732]
101436023  GRM6; metabotropic glutamate receptor 6 [KO:K04608]
101436226  [KO:K04607]
101436250  [KO:K05242]
101436887  DGKE; diacylglycerol kinase epsilon [KO:K00901] [EC:2.7.1.107]
101436995  DGKI; diacylglycerol kinase iota isoform X1 [KO:K00901] [EC:2.7.1.107]
101437043  AGPAT4; 1-acyl-sn-glycerol-3-phosphate acyltransferase delta [KO:K13523] [EC:2.3.1.51 2.3.1.-]
101437183  [KO:K08732]
101437562  LPAR3; lysophosphatidic acid receptor 3 [KO:K04294]
101437710  AGTR1; type-1 angiotensin II receptor [KO:K04166]
101437821  PTGFR; prostaglandin F2-alpha receptor [KO:K04262]
101438156  PLPP2; phospholipid phosphatase 2 isoform X1 [KO:K01080] [EC:3.1.3.4]
101438211  SYK; tyrosine-protein kinase SYK isoform X2 [KO:K05855] [EC:2.7.10.2]
101438260  SHC1; SHC-transforming protein 1 [KO:K06279]
101438487  [KO:K13509] [EC:2.3.1.51]
101438679  DGKD; diacylglycerol kinase delta isoform X1 [KO:K00901] [EC:2.7.1.107]
101439197  [KO:K08732]
101439293  RALA; ras-related protein Ral-A [KO:K07834]
101439353  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
101439384  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
101439429  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
101439928  [KO:K01080] [EC:3.1.3.4]
101440090  [KO:K08732]
101440125  PLPP1; phospholipid phosphatase 1 isoform X1 [KO:K01080] [EC:3.1.3.4]
101440135  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
101440141  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
101440815  CXCR1; C-X-C chemokine receptor type 1 [KO:K04175]
101441256  [KO:K05050]
101441273  LPAR6; lysophosphatidic acid receptor 6 [KO:K04273]
101441406  AVPR1A; vasopressin V1a receptor [KO:K04226]
101441641  CXCL8; interleukin-8 precursor [KO:K10030]
101441754  [KO:K01115] [EC:3.1.4.4]
101441858  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
101441865  [KO:K08732]
101442901  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101442950  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101443219  CYTH1; cytohesin-1 isoform X1 [KO:K18441]
101443396  [KO:K04513]
101443536  [KO:K08732]
101443644  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
101443761  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101443821  [KO:K08732]
101444276  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101444389  [KO:K08732]
101444730  GRM2; LOW QUALITY PROTEIN: metabotropic glutamate receptor 2 [KO:K04605]
101445050  CYTH4; cytohesin-4 [KO:K18441]
101445594  GRM5; metabotropic glutamate receptor 5 [KO:K04604]
101445813  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101445951  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
101445955  [KO:K08732]
101446137  ARF1; ADP-ribosylation factor 1 [KO:K07937]
101446304  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
101446801  TSC1; hamartin isoform X1 [KO:K07206]
101447287  [KO:K04603]
101447303  [KO:K08732]
101447321  SHC2; SHC-transforming protein 2 [KO:K17447]
101447803  GAB1; GRB2-associated-binding protein 1 isoform X3 [KO:K09593]
101447838  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101447959  DGKQ; diacylglycerol kinase theta [KO:K00901] [EC:2.7.1.107]
105744140  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
105745277  [KO:K08732]
105746538  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
111760411  [KO:K08090]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00165  Diacylglycerol
C00416  Phosphatidate
C00575  3',5'-Cyclic AMP
C00639  Prostaglandin F2alpha
C00681  1-Acyl-sn-glycerol 3-phosphate
C01245  D-myo-Inositol 1,4,5-trisphosphate
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06124  Sphingosine 1-phosphate
Reference
PMID:17245604
  Authors
Oude Weernink PA, Lopez de Jesus M, Schmidt M
  Title
Phospholipase D signaling: orchestration by PIP2 and small GTPases.
  Journal
Naunyn Schmiedebergs Arch Pharmacol 374:399-411 (2007)
DOI:10.1007/s00210-007-0131-4
Reference
PMID:21936578
  Authors
Selvy PE, Lavieri RR, Lindsley CW, Brown HA
  Title
Phospholipase D: enzymology, functionality, and chemical modulation.
  Journal
Chem Rev 111:6064-119 (2011)
DOI:10.1021/cr200296t
Reference
PMID:24995811
  Authors
Brandenburg LO, Pufe T, Koch T
  Title
Role of phospholipase d in g-protein coupled receptor function.
  Journal
Membranes (Basel) 4:302-18 (2014)
DOI:10.3390/membranes4030302
Reference
PMID:17054901
  Authors
Oude Weernink PA, Han L, Jakobs KH, Schmidt M
  Title
Dynamic phospholipid signaling by G protein-coupled receptors.
  Journal
Biochim Biophys Acta 1768:888-900 (2007)
DOI:10.1016/j.bbamem.2006.09.012
Reference
PMID:24990952
  Authors
Foster DA, Salloum D, Menon D, Frias MA
  Title
Phospholipase D and the maintenance of phosphatidic acid levels for regulation of mammalian target of rapamycin (mTOR).
  Journal
J Biol Chem 289:22583-8 (2014)
DOI:10.1074/jbc.R114.566091
Reference
PMID:16143829
  Authors
Jenkins GM, Frohman MA
  Title
Phospholipase D: a lipid centric review.
  Journal
Cell Mol Life Sci 62:2305-16 (2005)
DOI:10.1007/s00018-005-5195-z
Reference
PMID:19815110
  Authors
Metcalfe DD, Peavy RD, Gilfillan AM
  Title
Mechanisms of mast cell signaling in anaphylaxis.
  Journal
J Allergy Clin Immunol 124:639-46; quiz 647-8 (2009)
DOI:10.1016/j.jaci.2009.08.035
Reference
PMID:18936782
  Authors
Kalesnikoff J, Galli SJ
  Title
New developments in mast cell biology.
  Journal
Nat Immunol 9:1215-23 (2008)
DOI:10.1038/ni.f.216
Reference
PMID:12217395
  Authors
Cockcroft S, Way G, O'Luanaigh N, Pardo R, Sarri E, Fensome A
  Title
Signalling role for ARF and phospholipase D in mast cell exocytosis stimulated by crosslinking of the high affinity FcepsilonR1 receptor.
  Journal
Mol Immunol 38:1277-82 (2002)
DOI:10.1016/S0161-5890(02)00075-5
Reference
PMID:19410013
  Authors
Lee CS, Kim KL, Jang JH, Choi YS, Suh PG, Ryu SH
  Title
The roles of phospholipase D in EGFR signaling.
  Journal
Biochim Biophys Acta 1791:862-8 (2009)
DOI:10.1016/j.bbalip.2009.04.007
Reference
PMID:16622417
  Authors
Lee CS, Kim IS, Park JB, Lee MN, Lee HY, Suh PG, Ryu SH
  Title
The phox homology domain of phospholipase D activates dynamin GTPase activity and accelerates EGFR endocytosis.
  Journal
Nat Cell Biol 8:477-84 (2006)
DOI:10.1038/ncb1401
Reference
PMID:14769825
  Authors
Kam Y, Exton JH
  Title
Role of phospholipase D1 in the regulation of mTOR activity by lysophosphatidic acid.
  Journal
FASEB J 18:311-9 (2004)
DOI:10.1096/fj.03-0731com
Reference
PMID:9310372
  Authors
Kozawa O, Blume-Jensen P, Heldin CH, Ronnstrand L
  Title
Involvement of phosphatidylinositol 3'-kinase in stem-cell-factor-induced phospholipase D activation and arachidonic acid release.
  Journal
Eur J Biochem 248:149-55 (1997)
DOI:10.1111/j.1432-1033.1997.00149.x
Reference
PMID:11042115
  Authors
Slaaby R, Du G, Altshuller YM, Frohman MA, Seedorf K
  Title
Insulin-induced phospholipase D1 and phospholipase D2 activity in human embryonic kidney-293 cells mediated by the phospholipase C gamma and protein kinase C alpha signalling cascade.
  Journal
Biochem J 351 Pt 3:613-9 (2000)
DOI:10.1042/bj3510613
Reference
PMID:11991733
  Authors
Fahimi-Vahid M, Gosau N, Michalek C, Han L, Jakobs KH, Schmidt M, Roberts N, Avkiran M, Wieland T
  Title
Distinct signaling pathways mediate cardiomyocyte phospholipase D stimulation by endothelin-1 and thrombin.
  Journal
J Mol Cell Cardiol 34:441-53 (2002)
DOI:10.1006/jmcc.2002.1525
Reference
PMID:10666319
  Authors
Freeman EJ
  Title
The Ang II-induced growth of vascular smooth muscle cells involves a phospholipase D-mediated signaling mechanism.
  Journal
Arch Biochem Biophys 374:363-70 (2000)
DOI:10.1006/abbi.1999.1608
Reference
PMID:9119890
  Authors
Naro F, Donchenko V, Minotti S, Zolla L, Molinaro M, Adamo S
  Title
Role of phospholipase C and D signalling pathways in vasopressin-dependent myogenic differentiation.
  Journal
J Cell Physiol 171:34-42 (1997)
DOI:10.1002/(SICI)1097-4652(199704)171:1<34::AID-JCP5>3.0.CO;2-I
Reference
PMID:10807766
  Authors
Murdoch C, Finn A
  Title
Chemokine receptors and their role in inflammation and infectious diseases.
  Journal
Blood 95:3032-43 (2000)
Reference
PMID:8135758
  Authors
Sugiyama T, Sakai T, Nozawa Y, Oka N
  Title
Prostaglandin F2 alpha-stimulated phospholipase D activation in osteoblast-like MC3T3-E1 cells: involvement in sustained 1,2-diacylglycerol production.
  Journal
Biochem J 298 ( Pt 2):479-84 (1994)
DOI:10.1042/bj2980479
Reference
PMID:17210675
  Authors
Foster DA
  Title
Regulation of mTOR by phosphatidic acid?
  Journal
Cancer Res 67:1-4 (2007)
DOI:10.1158/0008-5472.CAN-06-3016
Reference
PMID:15310762
  Authors
Delon C, Manifava M, Wood E, Thompson D, Krugmann S, Pyne S, Ktistakis NT
  Title
Sphingosine kinase 1 is an intracellular effector of phosphatidic acid.
  Journal
J Biol Chem 279:44763-74 (2004)
DOI:10.1074/jbc.M405771200
Reference
PMID:23076158
  Authors
Park JB, Lee CS, Jang JH, Ghim J, Kim YJ, You S, Hwang D, Suh PG, Ryu SH
  Title
Phospholipase signalling networks in cancer.
  Journal
Nat Rev Cancer 12:782-92 (2012)
DOI:10.1038/nrc3379
Reference
PMID:19264150
  Authors
Foster DA
  Title
Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells.
  Journal
Biochim Biophys Acta 1791:949-55 (2009)
DOI:10.1016/j.bbalip.2009.02.009
Related
pathway
dnm00561  Glycerolipid metabolism
dnm04010  MAPK signaling pathway
dnm04014  Ras signaling pathway
dnm04020  Calcium signaling pathway
dnm04024  cAMP signaling pathway
dnm04071  Sphingolipid signaling pathway
dnm04144  Endocytosis
dnm04150  mTOR signaling pathway
dnm04151  PI3K-Akt signaling pathway
dnm04664  Fc epsilon RI signaling pathway
KO pathway
ko04072   

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