KEGG   PATHWAY: myb04072
Entry
myb04072                    Pathway                                
Name
Phospholipase D signaling pathway - Myotis brandtii (Brandt's 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
myb04072  Phospholipase D signaling pathway
myb04072

Organism
Myotis brandtii (Brandt's bat) [GN:myb]
Gene
102264252  EGF; epidermal growth factor [KO:K04357]
102253551  PDGFA; platelet derived growth factor subunit A [KO:K04359]
102239511  PDGFB; platelet derived growth factor subunit B [KO:K17386]
102248385  PDGFC; platelet derived growth factor C [KO:K05450]
102240259  PDGFD; platelet derived growth factor D [KO:K05450]
102250743  KITLG; KIT ligand [KO:K05461]
102254396  insulin [KO:K04526]
102257758  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102255326  PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
102241145  PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
102263655  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
102252005  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
102241832  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102245609  GAB1; GRB2 associated binding protein 1 [KO:K09593]
102256059  GAB2; GRB2 associated binding protein 2 [KO:K08091]
102245916  SHC1; SHC adaptor protein 1 [KO:K06279]
102251506  SHC2; SHC adaptor protein 2 [KO:K17447]
102245983  SHC3; SHC adaptor protein 3 [KO:K17448]
102239285  SHC4; SHC adaptor protein 4 [KO:K17449]
102251345  PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
102252301  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102259408  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102263667  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102244940  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102247606  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102261560  MRAS; muscle RAS oncogene homolog [KO:K07831]
102257602  RRAS2; related RAS viral (r-ras) oncogene homolog 2 [KO:K07830]
102240340  RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
102254804  RALA; RAS like proto-oncogene A [KO:K07834]
102259631  RALB; RAS like proto-oncogene B [KO:K07835]
102260487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102252921  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102239669  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102258430  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102253405  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102242302  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102254864  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102254191  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102251050  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102245381  TSC1; tuberous sclerosis 1 [KO:K07206]
102253389  TSC2; tuberous sclerosis 2 [KO:K07207]
102257160  RHEB; Ras homolog enriched in brain [KO:K07208]
102241670  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102244315  RHOA; ras homolog family member A [KO:K04513]
102239944  ARF1; ADP ribosylation factor 1 [KO:K07937]
102250274  ADP-ribosylation factor 1 [KO:K07937]
102249674  ADP-ribosylation factor 1 [KO:K07937]
102257649  uncharacterized LOC102257649 [KO:K07937]
102239161  ARF6; ADP ribosylation factor 6 [KO:K07941]
102248243  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102261553  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102253571  uncharacterized LOC102253571 [KO:K06856]
106724953  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
106725568  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
106725385  uncharacterized LOC106725385 [KO:K06856]
106726103  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
106726515  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
106726783  uncharacterized LOC106726783 [KO:K06856]
102251188  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
102252052  FCER1A; Fc fragment of IgE receptor Ia [KO:K08089]
102242504  MS4A2; membrane spanning 4-domains A2 [KO:K08090]
102246191  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
102242533  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
102243247  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
102260557  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102264100  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102239050  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102259120  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102260953  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
102242502  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102241902  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102248796  AGPAT2; 1-acylglycerol-3-phosphate O-acyltransferase 2 [KO:K13509] [EC:2.3.1.51]
102260060  AGPAT1; 1-acylglycerol-3-phosphate O-acyltransferase 1 [KO:K13509] [EC:2.3.1.51]
102258870  AGPAT3; 1-acylglycerol-3-phosphate O-acyltransferase 3 [KO:K13523] [EC:2.3.1.51 2.3.1.-]
102263031  AGPAT4; 1-acylglycerol-3-phosphate O-acyltransferase 4 [KO:K13523] [EC:2.3.1.51 2.3.1.-]
102244220  AGPAT5; 1-acylglycerol-3-phosphate O-acyltransferase 5 [KO:K19007] [EC:2.3.1.51]
102255740  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
102254173  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102254003  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102240696  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102245571  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102255250  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102245641  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102250383  PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:2.7.1.68]
102261636  PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:2.7.1.68]
102256140  PIP5K1C; phosphatidylinositol-4-phosphate 5-kinase type 1 gamma [KO:K00889] [EC:2.7.1.68]
102246856  DGKZ; diacylglycerol kinase zeta [KO:K00901] [EC:2.7.1.107]
102255385  DGKQ; diacylglycerol kinase theta [KO:K00901] [EC:2.7.1.107]
102254715  DGKA; diacylglycerol kinase alpha [KO:K00901] [EC:2.7.1.107]
102238850  DGKD; diacylglycerol kinase delta [KO:K00901] [EC:2.7.1.107]
102253513  DGKB; diacylglycerol kinase beta [KO:K00901] [EC:2.7.1.107]
102254924  DGKH; diacylglycerol kinase eta [KO:K00901] [EC:2.7.1.107]
102245595  DGKI; diacylglycerol kinase iota [KO:K00901] [EC:2.7.1.107]
102244943  DGKE; diacylglycerol kinase epsilon [KO:K00901] [EC:2.7.1.107]
102262940  DGKG; diacylglycerol kinase gamma [KO:K00901] [EC:2.7.1.107]
102240822  DGKK; diacylglycerol kinase kappa [KO:K00901] [EC:2.7.1.107]
102258225  PLPP2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
102250749  PLPP1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
102248875  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
102252492  F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5]
102262829  AGT; angiotensinogen [KO:K09821]
102243203  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
102245101  AGTR1; angiotensin II receptor type 1 [KO:K04166]
102249171  F2R; coagulation factor II thrombin receptor [KO:K03914]
102262324  GRM3; glutamate metabotropic receptor 3 [KO:K04606]
102258679  GRM4; glutamate metabotropic receptor 4 [KO:K04607]
102255799  GRM6; glutamate metabotropic receptor 6 [KO:K04608]
102240757  GRM7; glutamate metabotropic receptor 7 [KO:K04609]
102247202  metabotropic glutamate receptor 8 [KO:K04610]
102256646  GRM8; glutamate metabotropic receptor 8 [KO:K04610]
102245728  AVPR1A; arginine vasopressin receptor 1A [KO:K04226]
102262060  AVPR1B; arginine vasopressin receptor 1B [KO:K04227]
102259589  AVPR2; arginine vasopressin receptor 2 [KO:K04228]
102258769  LPAR1; lysophosphatidic acid receptor 1 [KO:K04289]
102246865  LPAR2; lysophosphatidic acid receptor 2 [KO:K04291]
102242469  LPAR3; lysophosphatidic acid receptor 3 [KO:K04294]
102246973  LPAR4; lysophosphatidic acid receptor 4 [KO:K04275]
102250139  LPAR5; lysophosphatidic acid receptor 5 [KO:K08390]
102251488  LPAR6; lysophosphatidic acid receptor 6 [KO:K04273]
102259225  PTGFR; prostaglandin F receptor [KO:K04262]
102255166  C-X-C chemokine receptor type 2-like [KO:K04175]
102246524  CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050]
102238655  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102254054  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102241255  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102240650  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102260289  GNA12; G protein subunit alpha 12 [KO:K04346]
102256791  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
102252423  GNA13; G protein subunit alpha 13 [KO:K04639]
102241723  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102246489  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102246179  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102239670  CYTH4; cytohesin 4 [KO:K18441]
102242400  CYTH3; cytohesin 3 [KO:K18441]
102250814  CYTH1; cytohesin 1 [KO:K18441]
102254634  CYTH2; cytohesin 2 [KO:K18441]
102252262  guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632]
102255448  neuroendocrine secretory protein 55 [KO:K04632]
102257679  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102260356  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102261014  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102247996  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102257731  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102248773  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102253549  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102249345  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102248953  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102257237  RAPGEF3; Rap guanine nucleotide exchange factor 3 [KO:K08014]
102262528  RAPGEF4; Rap guanine nucleotide exchange factor 4 [KO:K04351]
102259504  DNM3; dynamin 3 [KO:K01528] [EC:3.6.5.5]
102262334  DNM1; dynamin 1 [KO:K01528] [EC:3.6.5.5]
102252356  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
myb00561  Glycerolipid metabolism
myb04010  MAPK signaling pathway
myb04014  Ras signaling pathway
myb04020  Calcium signaling pathway
myb04024  cAMP signaling pathway
myb04071  Sphingolipid signaling pathway
myb04144  Endocytosis
myb04150  mTOR signaling pathway
myb04151  PI3K-Akt signaling pathway
myb04664  Fc epsilon RI signaling pathway
KO pathway
ko04072   
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