KEGG   PATHWAY: mna04072
Entry
mna04072                    Pathway                                
Name
Phospholipase D signaling pathway - Miniopterus natalensis (Natal long-fingered bat)
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
mna04072  Phospholipase D signaling pathway
mna04072

Organism
Miniopterus natalensis (Natal long-fingered bat) [GN:mna]
Gene
107534373  EGF; pro-epidermal growth factor [KO:K04357]
107543141  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
107531241  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
107527538  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
107532411  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
107526843  KITLG; kit ligand isoform X1 [KO:K05461]
107525996  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
107532710  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
107535230  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
107532733  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
107540632  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
107536618  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
107532524  GAB1; GRB2-associated-binding protein 1 [KO:K09593]
107524432  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
107543890  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
107538554  SHC2; SHC-transforming protein 2 [KO:K17447]
107529164  SHC3; SHC-transforming protein 3 [KO:K17448]
107535558  SHC4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449]
107529574  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
107525851  SOS2; son of sevenless homolog 2 [KO:K03099]
107541780  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107542351  HRAS; GTPase HRas isoform X1 [KO:K02833]
107525258  KRAS; GTPase KRas [KO:K07827]
107545303  NRAS; GTPase NRas [KO:K07828]
107532623  MRAS; ras-related protein M-Ras [KO:K07831]
107531795  RRAS; ras-related protein R-Ras [KO:K07829]
107546716  RRAS2; ras-related protein R-Ras2 isoform X1 [KO:K07830]
107524673  RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
107532781  RALA; ras-related protein Ral-A [KO:K07834]
107534635  RALB; ras-related protein Ral-B [KO:K07835]
107532628  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107538463  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
107541106  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107526728  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
107529317  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107535325  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
107542383  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107528331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107534199  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107524632  TSC1; hamartin [KO:K07206]
107533380  TSC2; tuberin isoform X1 [KO:K07207]
107524898  RHEB; GTP-binding protein Rheb [KO:K07208]
107540994  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
107529450  RHOA; transforming protein RhoA [KO:K04513]
107529920  ARF1; ADP-ribosylation factor 1 [KO:K07937]
107530284  ADP-ribosylation factor 2-like isoform X1 [KO:K07937]
107525849  ARF6; ADP-ribosylation factor 6 [KO:K07941]
107542131  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
107524904  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
107545176  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
107527650  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
107535097  FCER1G; LOW QUALITY PROTEIN: high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
107540684  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
107529171  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
107538300  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
107528068  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
107529520  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
107533526  phospholipase D1 [KO:K01115] [EC:3.1.4.4]
107546298  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
107536544  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
107536549  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
107536550  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
107536561  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
107535575  AGPAT2; 1-acyl-sn-glycerol-3-phosphate acyltransferase beta [KO:K13509] [EC:2.3.1.51]
107538983  AGPAT1; 1-acyl-sn-glycerol-3-phosphate acyltransferase alpha isoform X1 [KO:K13509] [EC:2.3.1.51]
107535729  AGPAT4; 1-acyl-sn-glycerol-3-phosphate acyltransferase delta [KO:K13523] [EC:2.3.1.51 2.3.1.-]
107537481  AGPAT3; 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma [KO:K13523] [EC:2.3.1.51 2.3.1.-]
107541968  AGPAT5; 1-acyl-sn-glycerol-3-phosphate acyltransferase epsilon [KO:K19007] [EC:2.3.1.51]
107536591  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
107531908  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
107534729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107533801  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
107525695  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107539122  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform X1 [KO:K00889] [EC:2.7.1.68]
107538124  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
107525631  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
107524123  DGKQ; diacylglycerol kinase theta [KO:K00901] [EC:2.7.1.107]
107527428  DGKG; diacylglycerol kinase gamma isoform X1 [KO:K00901] [EC:2.7.1.107]
107538212  DGKA; diacylglycerol kinase alpha isoform X1 [KO:K00901] [EC:2.7.1.107]
107541468  DGKK; diacylglycerol kinase kappa [KO:K00901] [EC:2.7.1.107]
107532728  DGKE; diacylglycerol kinase epsilon [KO:K00901] [EC:2.7.1.107]
107544150  DGKI; diacylglycerol kinase iota [KO:K00901] [EC:2.7.1.107]
107531381  DGKH; diacylglycerol kinase eta isoform X1 [KO:K00901] [EC:2.7.1.107]
107541720  DGKB; diacylglycerol kinase beta isoform X1 [KO:K00901] [EC:2.7.1.107]
107530326  DGKZ; diacylglycerol kinase zeta isoform X1 [KO:K00901] [EC:2.7.1.107]
107530748  DGKD; diacylglycerol kinase delta isoform X1 [KO:K00901] [EC:2.7.1.107]
107538563  PLPP2; phospholipid phosphatase 2 isoform X1 [KO:K01080] [EC:3.1.3.4]
107527147  PLPP1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
107530656  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
107530315  F2; prothrombin isoform X1 [KO:K01313] [EC:3.4.21.5]
107524243  AGT; angiotensinogen [KO:K09821]
107536288  AVP; vasopressin-neurophysin 2-copeptin [KO:K05242]
107534494  CXCL8; interleukin-8 [KO:K10030]
107544042  AGTR1; type-1 angiotensin II receptor [KO:K04166]
107531201  F2R; proteinase-activated receptor 1 [KO:K03914]
107540188  GRM2; metabotropic glutamate receptor 2 [KO:K04605]
107541756  GRM3; metabotropic glutamate receptor 3 [KO:K04606]
107545631  GRM4; metabotropic glutamate receptor 4 [KO:K04607]
107532400  GRM5; metabotropic glutamate receptor 5 [KO:K04604]
107529861  GRM6; LOW QUALITY PROTEIN: metabotropic glutamate receptor 6 [KO:K04608]
107534797  GRM7; metabotropic glutamate receptor 7 isoform X1 [KO:K04609]
107537364  GRM8; metabotropic glutamate receptor 8 [KO:K04610]
107527253  AVPR1A; vasopressin V1a receptor [KO:K04226]
107539423  AVPR1B; vasopressin V1b receptor [KO:K04227]
107538807  AVPR2; vasopressin V2 receptor [KO:K04228]
107537650  LPAR1; lysophosphatidic acid receptor 1 [KO:K04289]
107535357  LPAR2; lysophosphatidic acid receptor 2 [KO:K04291]
107543205  LPAR3; lysophosphatidic acid receptor 3 [KO:K04294]
107537244  LPAR4; lysophosphatidic acid receptor 4 [KO:K04275]
107544026  LPAR5; lysophosphatidic acid receptor 5 [KO:K08390]
107531401  LPAR6; lysophosphatidic acid receptor 6 [KO:K04273]
107540119  PTGFR; prostaglandin F2-alpha receptor [KO:K04262]
107524847  C-X-C chemokine receptor type 2 [KO:K04175]
107524751  CXCR2; C-X-C chemokine receptor type 2 [KO:K05050]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
107541162  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
107538557  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
107538305  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
107530834  PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:2.7.1.153]
107544506  PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
107544531  PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
107545251  CYTH4; cytohesin-4 [KO:K18441]
107532047  CYTH1; cytohesin-1 isoform X1 [KO:K18441]
107537598  CYTH3; cytohesin-3 [KO:K18441]
107531909  CYTH2; cytohesin-2 isoform X1 [KO:K18441]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
107528219  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
107531114  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351]
107536133  DNM1; LOW QUALITY PROTEIN: dynamin-1 [KO:K01528] [EC:3.6.5.5]
107543795  DNM3; dynamin-3 isoform X1 [KO:K01528] [EC:3.6.5.5]
107533288  DNM2; dynamin-2 isoform X1 [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
mna00561  Glycerolipid metabolism
mna04010  MAPK signaling pathway
mna04014  Ras signaling pathway
mna04020  Calcium signaling pathway
mna04024  cAMP signaling pathway
mna04071  Sphingolipid signaling pathway
mna04144  Endocytosis
mna04150  mTOR signaling pathway
mna04151  PI3K-Akt signaling pathway
mna04664  Fc epsilon RI signaling pathway
KO pathway
ko04072   
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