KEGG   PATHWAY: tup04072
Entry
tup04072                    Pathway                                
Name
Phospholipase D signaling pathway - Tupaia chinensis (Chinese tree shrew)
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
tup04072  Phospholipase D signaling pathway
tup04072

Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102490423  EGF; epidermal growth factor [KO:K04357]
102499235  PDGFA; platelet derived growth factor subunit A [KO:K04359]
102482500  PDGFB; platelet derived growth factor subunit B [KO:K17386]
102485007  PDGFD; platelet derived growth factor D [KO:K05450]
102487522  PDGFC; platelet derived growth factor C [KO:K05450]
102501429  KITLG; KIT ligand [KO:K05461]
102481191  INS; insulin [KO:K04526]
102485304  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102488187  PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
102492413  PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
102489301  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
102469167  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
102493080  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102497468  GAB1; GRB2 associated binding protein 1 [KO:K09593]
102490988  GAB2; GRB2 associated binding protein 2 [KO:K08091]
102481002  SHC1; SHC adaptor protein 1 [KO:K06279]
102481863  SHC2; SHC adaptor protein 2 [KO:K17447]
102472295  SHC3; SHC adaptor protein 3 [KO:K17448]
102479734  SHC4; SHC adaptor protein 4 [KO:K17449]
102485136  PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
102498455  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
102494629  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102477222  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102468234  MRAS; muscle RAS oncogene homolog [KO:K07831]
102491386  RRAS; related RAS viral (r-ras) oncogene homolog [KO:K07829]
106734036  ras-related protein R-Ras2-like [KO:K07830]
102496329  RRAS2; ras-related protein R-Ras2 [KO:K07830]
102479691  RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
102481337  RALA; RAS like proto-oncogene A [KO:K07834]
102486756  RALB; RAS like proto-oncogene B [KO:K07835]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106736453  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102483474  TSC1; tuberous sclerosis 1 [KO:K07206]
102484276  TSC2; tuberous sclerosis 2 [KO:K07207]
102502516  RHEB; Ras homolog enriched in brain [KO:K07208]
102485262  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102487039  RHOA; ras homolog family member A [KO:K04513]
102502051  ARF1; ADP-ribosylation factor 1 [KO:K07937]
102476416  ARF6; ADP ribosylation factor 6 [KO:K07941]
102469651  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102483786  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102473679  uncharacterized LOC102473679 [KO:K06856]
102498935  uncharacterized LOC102498935 [KO:K06856]
106733485  uncharacterized LOC106733485 [KO:K06856]
102468324  FCER1A; Fc fragment of IgE receptor Ia [KO:K08089]
102468334  MS4A2; membrane spanning 4-domains A2 [KO:K08090]
102503197  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
102498676  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
102472653  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
102495954  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102495205  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102499889  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102473333  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
102470223  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
102471767  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102472618  JMJD7; jmjC domain-containing protein 7 [KO:K16342] [EC:3.1.1.4]
102470647  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102477396  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102485189  AGPAT1; 1-acylglycerol-3-phosphate O-acyltransferase 1 [KO:K13509] [EC:2.3.1.51]
102482776  AGPAT2; 1-acylglycerol-3-phosphate O-acyltransferase 2 [KO:K13509] [EC:2.3.1.51]
102500712  AGPAT4; 1-acylglycerol-3-phosphate O-acyltransferase 4 [KO:K13523] [EC:2.3.1.51 2.3.1.-]
102479882  AGPAT3; 1-acylglycerol-3-phosphate O-acyltransferase 3 [KO:K13523] [EC:2.3.1.51 2.3.1.-]
102498077  AGPAT5; 1-acylglycerol-3-phosphate O-acyltransferase 5 [KO:K19007] [EC:2.3.1.51]
102471518  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102476140  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102483700  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102488955  PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:2.7.1.68]
102497135  PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:2.7.1.68]
102470898  PIP5K1C; phosphatidylinositol-4-phosphate 5-kinase type 1 gamma [KO:K00889] [EC:2.7.1.68]
102472793  DGKI; diacylglycerol kinase iota [KO:K00901] [EC:2.7.1.107]
102468672  DGKQ; diacylglycerol kinase theta [KO:K00901] [EC:2.7.1.107]
102497040  DGKZ; diacylglycerol kinase zeta [KO:K00901] [EC:2.7.1.107]
102498108  DGKE; diacylglycerol kinase epsilon [KO:K00901] [EC:2.7.1.107]
102498793  DGKH; diacylglycerol kinase eta [KO:K00901] [EC:2.7.1.107]
102495834  DGKK; diacylglycerol kinase kappa [KO:K00901] [EC:2.7.1.107]
102497667  DGKA; diacylglycerol kinase alpha [KO:K00901] [EC:2.7.1.107]
102473594  DGKG; diacylglycerol kinase gamma [KO:K00901] [EC:2.7.1.107]
102488271  DGKB; diacylglycerol kinase beta [KO:K00901] [EC:2.7.1.107]
102473856  DGKD; diacylglycerol kinase delta [KO:K00901] [EC:2.7.1.107]
102500387  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
102499580  PLPP1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
102489550  PLPP2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
102468231  F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5]
102471092  AGT; angiotensinogen [KO:K09821]
102502924  AVP; arginine vasopressin [KO:K05242]
102471344  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
102469571  AGTR1; angiotensin II receptor type 1 [KO:K04166]
102485895  F2R; coagulation factor II thrombin receptor [KO:K03914]
102479064  GRM1; glutamate metabotropic receptor 1 [KO:K04603]
102474413  GRM2; glutamate metabotropic receptor 2 [KO:K04605]
102483840  GRM3; glutamate metabotropic receptor 3 [KO:K04606]
102486954  GRM5; glutamate metabotropic receptor 5 [KO:K04604]
102486281  GRM6; glutamate metabotropic receptor 6 [KO:K04608]
102478241  GRM7; glutamate metabotropic receptor 7 [KO:K04609]
102479399  GRM8; glutamate metabotropic receptor 8 [KO:K04610]
102480521  metabotropic glutamate receptor 8-like [KO:K04610]
102499356  AVPR1A; arginine vasopressin receptor 1A [KO:K04226]
102479096  AVPR1B; arginine vasopressin receptor 1B [KO:K04227]
102502524  AVPR2; arginine vasopressin receptor 2 [KO:K04228]
102503029  LPAR1; lysophosphatidic acid receptor 1 [KO:K04289]
102502351  LPAR2; lysophosphatidic acid receptor 2 [KO:K04291]
102495978  LPAR3; lysophosphatidic acid receptor 3 [KO:K04294]
102500888  LPAR4; lysophosphatidic acid receptor 4 [KO:K04275]
102491630  LPAR5; lysophosphatidic acid receptor 5 [KO:K08390]
102494278  LPAR6; lysophosphatidic acid receptor 6 [KO:K04273]
102487637  PTGFR; prostaglandin F receptor [KO:K04262]
102484375  CXCR1; C-X-C motif chemokine receptor 1 [KO:K04175]
102484805  CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050]
102477438  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102476196  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102472532  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102492903  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102501406  GNA12; G protein subunit alpha 12 [KO:K04346]
102481841  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
102488219  GNA13; G protein subunit alpha 13 [KO:K04639]
102472442  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102470324  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102485065  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102469284  CYTH3; cytohesin 3 [KO:K18441]
102478515  CYTH2; cytohesin 2 [KO:K18441]
102485408  CYTH1; cytohesin 1 [KO:K18441]
102496101  CYTH4; cytohesin 4 [KO:K18441]
102489563  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102501321  neuroendocrine secretory protein 55 [KO:K04632]
102468873  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102492353  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102477532  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102490273  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102490639  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102468478  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102496578  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102472317  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102477344  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102502265  RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
102485451  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
102477586  DNM1; dynamin 1 [KO:K01528] [EC:3.6.5.5]
102469489  DNM3; dynamin 3 [KO:K01528] [EC:3.6.5.5]
102473910  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
tup00561  Glycerolipid metabolism
tup04010  MAPK signaling pathway
tup04014  Ras signaling pathway
tup04020  Calcium signaling pathway
tup04024  cAMP signaling pathway
tup04071  Sphingolipid signaling pathway
tup04144  Endocytosis
tup04150  mTOR signaling pathway
tup04151  PI3K-Akt signaling pathway
tup04664  Fc epsilon RI signaling pathway
KO pathway
ko04072   
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