KEGG   PATHWAY: pvp04072
Entry
pvp04072                    Pathway                                
Name
Phospholipase D signaling pathway - Pteropus vampyrus (large flying fox)
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
pvp04072  Phospholipase D signaling pathway
pvp04072

Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288310  CYTH4; cytohesin-4 [KO:K18441]
105288668  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
105288669  PLA2G4F; cytosolic phospholipase A2 zeta isoform X2 [KO:K16342] [EC:3.1.1.4]
105288781  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105288785  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
105288787  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
105288811  SHC4; SHC-transforming protein 4 [KO:K17449]
105288850  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105289056  PTGFR; prostaglandin F2-alpha receptor [KO:K04262]
105289073  LPAR3; lysophosphatidic acid receptor 3 isoform X2 [KO:K04294]
105289236  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289441  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
105289813  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105289863  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
105290015  DGKZ; diacylglycerol kinase zeta isoform X8 [KO:K00901] [EC:2.7.1.107]
105290023  F2; prothrombin isoform X2 [KO:K01313] [EC:3.4.21.5]
105290355  RAPGEF4; rap guanine nucleotide exchange factor 4 [KO:K04351]
105291073  [KO:K04175]
105291074  CXCR2; C-X-C chemokine receptor type 2 [KO:K05050]
105291261  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290]
105291351  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
105291564  GAB1; GRB2-associated-binding protein 1 isoform X7 [KO:K09593]
105291671  DGKI; diacylglycerol kinase iota [KO:K00901] [EC:2.7.1.107]
105291755  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
105292087  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105292199  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
105292221  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
105292339  CXCL8; interleukin-8 [KO:K10030]
105292949  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105293045  EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357]
105293228  KITLG; kit ligand isoform X1 [KO:K05461]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105293381  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
105293449  CYTH1; cytohesin-1 [KO:K18441]
105293773  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
105293808  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294211  GRM5; metabotropic glutamate receptor 5 [KO:K04604]
105294429  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105294560  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
105294593  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
105294624  CYTH3; cytohesin-3 [KO:K18441]
105294820  DNM1; dynamin-1 isoform X5 [KO:K01528] [EC:3.6.5.5]
105294889  GRM3; metabotropic glutamate receptor 3 isoform X1 [KO:K04606]
105294948  AGTR1; type-1 angiotensin II receptor [KO:K04166]
105295051  DGKB; diacylglycerol kinase beta [KO:K00901] [EC:2.7.1.107]
105295052  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
105295132  GRM2; metabotropic glutamate receptor 2 [KO:K04605]
105295260  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
105295316  LPAR1; lysophosphatidic acid receptor 1 isoform X1 [KO:K04289]
105295420  DGKE; diacylglycerol kinase epsilon [KO:K00901] [EC:2.7.1.107]
105295963  LPAR5; lysophosphatidic acid receptor 5 [KO:K08390]
105296083  [KO:K04632]
105296141  RALB; ras-related protein Ral-B isoform X2 [KO:K07835]
105296379  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
105296521  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296556  LPAR2; lysophosphatidic acid receptor 2 [KO:K04291]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105297140  [KO:K02649]
105297442  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
105297498  RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X2 [KO:K08014]
105297518  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105297599  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
105297699  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
105297702  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105297846  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105298078  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
105298463  DGKH; diacylglycerol kinase eta isoform X4 [KO:K00901] [EC:2.7.1.107]
105298624  AGPAT2; 1-acyl-sn-glycerol-3-phosphate acyltransferase beta [KO:K13509] [EC:2.3.1.51]
105298655  TSC1; hamartin isoform X1 [KO:K07206]
105298674  RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298737  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105298946  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299308  [KO:K05242]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299436  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
105299444  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105299581  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105299800  DNM3; dynamin-3 isoform X3 [KO:K01528] [EC:3.6.5.5]
105299957  ARF1; ADP-ribosylation factor 1 [KO:K07937]
105300006  GRM6; metabotropic glutamate receptor 6 [KO:K04608]
105300022  LPAR6; lysophosphatidic acid receptor 6 [KO:K04273]
105300159  [KO:K04456] [EC:2.7.11.1]
105300248  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
105300265  SHC3; SHC-transforming protein 3 [KO:K17448]
105300332  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
105300363  GRM7; metabotropic glutamate receptor 7 isoform X1 [KO:K04609]
105300480  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma [KO:K00889] [EC:2.7.1.68]
105300650  [KO:K04227]
105300730  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
105300735  [KO:K04227]
105301005  GRM4; metabotropic glutamate receptor 4 isoform X1 [KO:K04607]
105301250  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105301479  RRAS2; ras-related protein R-Ras2 [KO:K07830]
105301735  RRAS; ras-related protein R-Ras [KO:K07829]
105301772  SPHK2; LOW QUALITY PROTEIN: sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
105301774  CYTH2; cytohesin-2 isoform X1 [KO:K18441]
105301865  DGKQ; diacylglycerol kinase theta [KO:K00901] [EC:2.7.1.107]
105302086  [KO:K04226]
105302096  [KO:K04226]
105302193  F2R; proteinase-activated receptor 1 [KO:K03914]
105302255  PLPP2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
105302278  SHC2; SHC-transforming protein 2 [KO:K17447]
105302383  RHOA; transforming protein RhoA [KO:K04513]
105302524  AVPR2; vasopressin V2 receptor [KO:K04228]
105302603  DGKA; diacylglycerol kinase alpha isoform X1 [KO:K00901] [EC:2.7.1.107]
105303040  AGPAT3; 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma [KO:K13523] [EC:2.3.1.51 2.3.1.-]
105303095  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105303207  RALA; ras-related protein Ral-A [KO:K07834]
105303335  TSC2; LOW QUALITY PROTEIN: tuberin [KO:K07207]
105303397  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
105303777  RHEB; GTP-binding protein Rheb [KO:K07208]
105303834  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform X1 [KO:K00889] [EC:2.7.1.68]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105305030  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
105305273  AGPAT5; 1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon [KO:K19007] [EC:2.3.1.51]
105305282  AGPAT1; 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha isoform X1 [KO:K13509] [EC:2.3.1.51]
105305660  DNM2; dynamin-2 [KO:K23484]
105305680  AGPAT4; 1-acyl-sn-glycerol-3-phosphate acyltransferase delta [KO:K13523] [EC:2.3.1.51 2.3.1.-]
105305810  PLPP1; phospholipid phosphatase 1 isoform X1 [KO:K01080] [EC:3.1.3.4]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306002  DGKD; diacylglycerol kinase delta [KO:K00901] [EC:2.7.1.107]
105306010  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
105306022  AGT; angiotensinogen [KO:K09821]
105306141  [KO:K04361] [EC:2.7.10.1]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105307100  LPAR4; lysophosphatidic acid receptor 4 [KO:K04275]
105307133  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307438  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105307815  DGKG; diacylglycerol kinase gamma isoform X1 [KO:K00901] [EC:2.7.1.107]
105308299  [KO:K08041] [EC:4.6.1.1]
105308953  [KO:K07831]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309400  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105309535  SOS2; son of sevenless homolog 2 [KO:K03099]
105309567  ARF6; ADP-ribosylation factor 6 [KO:K07941]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105309828  [KO:K07293] [EC:3.1.3.48]
105309966  DGKK; diacylglycerol kinase kappa [KO:K00901] [EC:2.7.1.107]
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
pvp00561  Glycerolipid metabolism
pvp04010  MAPK signaling pathway
pvp04014  Ras signaling pathway
pvp04020  Calcium signaling pathway
pvp04024  cAMP signaling pathway
pvp04071  Sphingolipid signaling pathway
pvp04144  Endocytosis
pvp04150  mTOR signaling pathway
pvp04151  PI3K-Akt signaling pathway
pvp04664  Fc epsilon RI signaling pathway
KO pathway
ko04072   

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