KEGG   PATHWAY: epz04072
Entry
epz04072                    Pathway                                
Name
Phospholipase D signaling pathway - Equus przewalskii (Przewalski's horse)
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
epz04072  Phospholipase D signaling pathway
epz04072

Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103543333  pro-epidermal growth factor-like [KO:K04357]
103555992  PDGFA; platelet derived growth factor subunit A [KO:K04359]
103565679  PDGFB; platelet derived growth factor subunit B [KO:K17386]
103547315  PDGFC; platelet derived growth factor C [KO:K05450]
103558709  PDGFD; platelet derived growth factor D [KO:K05450]
103555517  KITLG; KIT ligand [KO:K05461]
103567614  INS; insulin [KO:K04526]
103560128  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103552305  PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
103549125  PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
103554972  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
103546580  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103558534  GAB1; GRB2 associated binding protein 1 [KO:K09593]
103543515  GRB2-associated-binding protein 2 [KO:K08091]
103552865  SHC1; SHC adaptor protein 1 [KO:K06279]
103542441  SHC2; SHC adaptor protein 2 [KO:K17447]
103552516  SHC3; SHC adaptor protein 3 [KO:K17448]
103551857  SHC4; SHC adaptor protein 4 [KO:K17449]
103557133  PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
103558567  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
103553088  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103556123  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103567332  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103546629  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103552675  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103550584  MRAS; muscle RAS oncogene homolog [KO:K07831]
103567387  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
103553681  RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
103544618  ral guanine nucleotide dissociation stimulator-like [KO:K08732]
103563476  RALA; RAS like proto-oncogene A [KO:K07834]
103565218  RALB; RAS like proto-oncogene B [KO:K07835]
103549076  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103554655  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform-like [KO:K00922] [EC:2.7.1.153]
103552150  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103548220  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103551868  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103561550  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103560497  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103540249  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103555421  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103553676  TSC1; tuberous sclerosis 1 [KO:K07206]
103566788  TSC2; tuberous sclerosis 2 [KO:K07207]
103552237  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103553409  RHOA; ras homolog family member A [KO:K04513]
103565871  ARF1; ADP ribosylation factor 1 [KO:K07937]
103552911  ADP-ribosylation factor 2 [KO:K07937]
103556125  ARF6; ADP ribosylation factor 6 [KO:K07941]
103562208  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103558212  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
103562625  uncharacterized LOC103562625 [KO:K06856]
103562621  putative V-set and immunoglobulin domain-containing protein 7 [KO:K06856]
103553939  FCER1A; Fc fragment of IgE receptor Ia [KO:K08089]
103553483  MS4A2; membrane spanning 4-domains A2 [KO:K08090]
103554497  high affinity immunoglobulin epsilon receptor subunit gamma-like [KO:K07983]
103559990  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
103547543  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
103565660  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
103546360  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
103560664  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
103549946  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
103549947  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
103549950  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
103549953  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
103560072  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
103566649  AGPAT1; 1-acylglycerol-3-phosphate O-acyltransferase 1 [KO:K13509] [EC:2.3.1.51]
103567693  AGPAT2; 1-acylglycerol-3-phosphate O-acyltransferase 2 [KO:K13509] [EC:2.3.1.51]
103561235  AGPAT3; 1-acylglycerol-3-phosphate O-acyltransferase 3 [KO:K13523] [EC:2.3.1.51 2.3.1.-]
103556186  AGPAT4; 1-acylglycerol-3-phosphate O-acyltransferase 4 [KO:K13523] [EC:2.3.1.51 2.3.1.-]
103547368  AGPAT5; 1-acylglycerol-3-phosphate O-acyltransferase 5 [KO:K19007] [EC:2.3.1.51]
103540021  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
103541302  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
103554541  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103549630  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103543290  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103546289  PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:2.7.1.68]
103547657  PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:2.7.1.68]
103543283  phosphatidylinositol 4-phosphate 5-kinase type-1 gamma-like [KO:K00889] [EC:2.7.1.68]
103550761  DGKE; diacylglycerol kinase epsilon [KO:K00901] [EC:2.7.1.107]
103555153  DGKI; diacylglycerol kinase iota [KO:K00901] [EC:2.7.1.107]
103566899  DGKZ; diacylglycerol kinase zeta [KO:K00901] [EC:2.7.1.107]
103560343  DGKH; diacylglycerol kinase eta [KO:K00901] [EC:2.7.1.107]
103551018  DGKB; diacylglycerol kinase beta [KO:K00901] [EC:2.7.1.107]
103541261  DGKK; diacylglycerol kinase kappa [KO:K00901] [EC:2.7.1.107]
103560195  DGKA; diacylglycerol kinase alpha [KO:K00901] [EC:2.7.1.107]
103565374  DGKQ; diacylglycerol kinase theta [KO:K00901] [EC:2.7.1.107]
103556371  diacylglycerol kinase gamma [KO:K00901] [EC:2.7.1.107]
103555976  DGKD; diacylglycerol kinase delta [KO:K00901] [EC:2.7.1.107]
103544352  lipid phosphate phosphohydrolase 1 [KO:K01080] [EC:3.1.3.4]
103541495  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
103545237  lipid phosphate phosphohydrolase 2-like [KO:K01080] [EC:3.1.3.4]
103566907  F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5]
103561130  AGT; angiotensinogen [KO:K09821]
103566768  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
103558752  AGTR1; angiotensin II receptor type 1 [KO:K04166]
103540011  F2R; coagulation factor II thrombin receptor [KO:K03914]
103564725  GRM1; glutamate metabotropic receptor 1 [KO:K04603]
103566922  GRM2; glutamate metabotropic receptor 2 [KO:K04605]
103562299  GRM3; glutamate metabotropic receptor 3 [KO:K04606]
103547854  GRM5; glutamate metabotropic receptor 5 [KO:K04604]
103540009  GRM6; glutamate metabotropic receptor 6 [KO:K04608]
103549493  GRM7; glutamate metabotropic receptor 7 [KO:K04609]
103546392  GRM8; glutamate metabotropic receptor 8 [KO:K04610]
103552372  AVPR1A; arginine vasopressin receptor 1A [KO:K04226]
103553836  AVPR1B; arginine vasopressin receptor 1B [KO:K04227]
103546686  LPAR1; lysophosphatidic acid receptor 1 [KO:K04289]
103561322  LPAR2; lysophosphatidic acid receptor 2 [KO:K04291]
103562992  LPAR3; lysophosphatidic acid receptor 3 [KO:K04294]
103561874  LPAR4; lysophosphatidic acid receptor 4 [KO:K04275]
103547006  LPAR5; lysophosphatidic acid receptor 5 [KO:K08390]
103549434  LPAR6; lysophosphatidic acid receptor 6 [KO:K04273]
103567001  PTGFR; prostaglandin F receptor [KO:K04262]
103564146  C-X-C chemokine receptor type 2-like [KO:K04175]
103564145  CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050]
103562440  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103559733  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103561633  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103542193  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103549418  GNA12; G protein subunit alpha 12 [KO:K04346]
103550428  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
103553497  GNA13; G protein subunit alpha 13 [KO:K04639]
103557800  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
103564501  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
103564503  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
103551448  CYTH1; cytohesin 1 [KO:K18441]
103555775  CYTH3; cytohesin 3 [KO:K18441]
103541382  CYTH2; cytohesin 2 [KO:K18441]
103564459  CYTH4; cytohesin 4 [KO:K18441]
103565402  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103547036  neuroendocrine secretory protein 55 [KO:K04632]
103550430  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103562505  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
103547823  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103561050  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103563830  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103563634  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103556685  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103565019  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
103567623  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103553014  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103546793  RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
103559592  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
103554258  DNM3; dynamin 3 [KO:K01528] [EC:3.6.5.5]
103565071  dynamin-3-like [KO:K01528] [EC:3.6.5.5]
103550849  DNM1; dynamin 1 [KO:K01528] [EC:3.6.5.5]
103562422  DNM2; dynamin 2 [KO:K23484] [EC:3.6.5.5]
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
epz00561  Glycerolipid metabolism
epz04010  MAPK signaling pathway
epz04014  Ras signaling pathway
epz04020  Calcium signaling pathway
epz04024  cAMP signaling pathway
epz04071  Sphingolipid signaling pathway
epz04144  Endocytosis
epz04150  mTOR signaling pathway
epz04151  PI3K-Akt signaling pathway
epz04664  Fc epsilon RI signaling pathway
KO pathway
ko04072   
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