KEGG   PATHWAY: epz04015
Entry
epz04015                    Pathway                                
Name
Rap1 signaling pathway - Equus przewalskii (Przewalski's horse)
Description
Rap1 is a small GTPase that controls diverse processes, such as cell adhesion, cell-cell junction formation and cell polarity. Like all G proteins, Rap1 cycles between an inactive GDP-bound and an active GTP-bound conformation. A variety of extracellular signals control this cycle through the regulation of several unique guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). Rap1 plays a dominant role in the control of cell-cell and cell-matrix interactions by regulating the function of integrins and other adhesion molecules in various cell types. Rap1 also regulates MAP kinase (MAPK) activity in a manner highly dependent on the context of cell types.
Class
Environmental Information Processing; Signal transduction
Pathway map
epz04015  Rap1 signaling pathway
epz04015

Other DBs
GO: 0007264
Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103547802  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
103558687  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
103550584  MRAS; muscle RAS oncogene homolog [KO:K07831]
103561104  RAPGEF5; Rap guanine nucleotide exchange factor 5 [KO:K08019]
103563200  DOCK4; dedicator of cytokinesis 4 [KO:K17697]
103563588  GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208]
103555146  GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209]
103549904  GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210]
103548885  CALML5; calmodulin like 5 [KO:K02183]
103548886  CALML3; calmodulin like 3 [KO:K02183]
103549905  CALM1; calmodulin 1 [KO:K02183]
103558105  CALM2; calmodulin 2 [KO:K02183]
103564053  calmodulin-like protein 4 [KO:K02183]
103544963  calmodulin-alpha-like [KO:K02183]
103567415  CALML6; calmodulin like 6 [KO:K02183]
103540011  F2R; coagulation factor II thrombin receptor [KO:K03914]
103543162  F2RL3; F2R like thrombin/trypsin receptor 3 [KO:K04236]
103551781  P2RY1; purinergic receptor P2Y1 [KO:K04270]
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]
103561852  ADORA2A; adenosine A2a receptor [KO:K04266]
103560476  ADORA2B; adenosine A2b receptor [KO:K04267]
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]
103553450  GNAQ; G protein subunit alpha q [KO:K04634]
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]
103558532  RASGRP3; RAS guanyl releasing protein 3 [KO:K12362]
103565063  RASGRP2; RAS guanyl releasing protein 2 [KO:K12361]
103543333  pro-epidermal growth factor-like [KO:K04357]
103550265  FGF1; fibroblast growth factor 1 [KO:K18496]
103542783  FGF18; fibroblast growth factor 18 [KO:K04358]
103549913  FGF5; fibroblast growth factor 5 [KO:K04358]
103551851  FGF7; fibroblast growth factor 7 [KO:K04358]
103551394  FGF8; fibroblast growth factor 8 [KO:K04358]
103568034  FGF17; fibroblast growth factor 17 [KO:K04358]
103542556  fibroblast growth factor 4-like [KO:K04358]
103556855  FGF20; fibroblast growth factor 20 [KO:K04358]
103557835  FGF6; fibroblast growth factor 6 [KO:K04358]
103558900  FGF9; fibroblast growth factor 9 [KO:K04358]
103544754  FGF22; fibroblast growth factor 22 [KO:K04358]
103559741  FGF10; fibroblast growth factor 10 [KO:K04358]
103544063  FGF3; fibroblast growth factor 3 [KO:K04358]
103543606  fibroblast growth factor 16 [KO:K04358]
103542877  FGF19; fibroblast growth factor 19 [KO:K22603]
103553325  FGF21; fibroblast growth factor 21 [KO:K22429]
103567716  FGF23; fibroblast growth factor 23 [KO:K22428]
103547744  NGF; nerve growth factor [KO:K02582]
103567614  INS; insulin [KO:K04526]
103549360  IGF1; insulin like growth factor 1 [KO:K05459]
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]
103557529  CSF1; colony stimulating factor 1 [KO:K05453]
103555517  KITLG; KIT ligand [KO:K05461]
103548136  VEGFA; vascular endothelial growth factor A [KO:K05448]
103542197  VEGFB; vascular endothelial growth factor B [KO:K16858]
103551779  VEGFC; vascular endothelial growth factor C [KO:K05449]
103564509  VEGFD; vascular endothelial growth factor D [KO:K05449]
103563173  HGF; hepatocyte growth factor [KO:K05460]
103553227  ANGPT1; angiopoietin 1 [KO:K05465]
103547367  ANGPT2; angiopoietin 2 [KO:K05466]
103556914  ANGPT4; angiopoietin 4 [KO:K05467]
103552854  EFNA1; ephrin A1 [KO:K05462]
103552855  EFNA4; ephrin A4 [KO:K05462]
103552874  EFNA3; ephrin A3 [KO:K05462]
103540090  EFNA5; ephrin A5 [KO:K05462]
103560128  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103560266  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
103547114  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
103556997  FGFR3; fibroblast growth factor receptor 3 [KO:K05094] [EC:2.7.10.1]
103557327  FGFR4; fibroblast growth factor receptor 4 [KO:K05095] [EC:2.7.10.1]
103551072  NGFR; nerve growth factor receptor [KO:K02583]
103559577  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [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]
103560147  macrophage colony-stimulating factor 1 receptor-like [KO:K05090] [EC:2.7.10.1]
103554972  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
103561902  FLT1; fms related tyrosine kinase 1 [KO:K05096] [EC:2.7.10.1]
103566205  FLT4; fms related tyrosine kinase 4 [KO:K05097] [EC:2.7.10.1]
103554974  KDR; kinase insert domain receptor [KO:K05098] [EC:2.7.10.1]
103562070  MET; MET proto-oncogene, receptor tyrosine kinase [KO:K05099] [EC:2.7.10.1]
103550275  TEK; TEK receptor tyrosine kinase [KO:K05121] [EC:2.7.10.1]
103552924  EPHA2; EPH receptor A2 [KO:K05103] [EC:2.7.10.1]
103547531  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
103543614  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
103553650  RAPGEF1; Rap guanine nucleotide exchange factor 1 [KO:K06277]
103553038  BCAR1; BCAR1, Cas family scaffolding protein [KO:K05726]
103549722  CDH1; cadherin 1 [KO:K05689]
103552888  CTNNB1; catenin beta 1 [KO:K02105]
103559161  MAGI1; membrane associated guanylate kinase, WW and PDZ domain containing 1 [KO:K05631]
103559766  MAGI3; membrane associated guanylate kinase, WW and PDZ domain containing 3 [KO:K06112]
103545519  RAPGEF2; Rap guanine nucleotide exchange factor 2 [KO:K08018]
103565155  rap guanine nucleotide exchange factor 6 [KO:K08020]
103541108  uncharacterized LOC103541108 [KO:K10784]
103567401  uncharacterized LOC103567401 [KO:K10784]
103564100  uncharacterized LOC103564100 [KO:K10785]
103542083  uncharacterized LOC103542083 [KO:K10785]
103562729  LAT; linker for activation of T-cells [KO:K07362]
103555258  FYB; FYN binding protein [KO:K17698]
103541962  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103557982  SKAP1; src kinase associated phosphoprotein 1 [KO:K17699]
103562208  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103558165  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103556196  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
103552099  PRKD1; protein kinase D1 [KO:K06070] [EC:2.7.11.13]
103548402  PRKD3; protein kinase D3 [KO:K06070] [EC:2.7.11.13]
103542502  serine/threonine-protein kinase D2 [KO:K06070] [EC:2.7.11.13]
103567933  DRD2; dopamine receptor D2 [KO:K04145]
103549524  CNR1; cannabinoid receptor 1 [KO:K04277]
103552141  guanine nucleotide-binding protein G(i) subunit alpha-1-like [KO:K04630]
103553052  GNAI3; G protein subunit alpha i3 [KO:K04630]
103557343  GNAI2; G protein subunit alpha i2 [KO:K04630]
103555391  GNAO1; G protein subunit alpha o1 [KO:K04534]
103562687  RAP1GAP; RAP1 GTPase activating protein [KO:K17700]
103541079  signal-induced proliferation-associated 1-like protein 1 [KO:K17701]
103543691  SIPA1; signal-induced proliferation-associated 1 [KO:K08013]
103550968  SIPA1L2; signal induced proliferation associated 1 like 2 [KO:K17702]
103552490  SIPA1L3; signal induced proliferation associated 1 like 3 [KO:K17703]
103559169  ID1; inhibitor of DNA binding 1, HLH protein [KO:K04680]
103556716  THBS1; thrombospondin 1 [KO:K16857]
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]
103552260  ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
103564464  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
103551104  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
103565481  APBB1IP; amyloid beta precursor protein binding family B member 1 interacting protein [KO:K17704]
103552581  TLN2; talin 2 [KO:K06271]
103560301  TLN1; talin 1 [KO:K06271]
103551206  ITGA2B; integrin subunit alpha 2b [KO:K06476]
103560746  ITGB3; integrin subunit beta 3 [KO:K06493]
103547830  PFN4; profilin family member 4 [KO:K05759]
103539970  PFN3; profilin 3 [KO:K05759]
103543790  profilin-1-like [KO:K05759]
103560657  PFN1; profilin 1 [KO:K05759]
103563312  PFN2; profilin 2 [KO:K05759]
103566352  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
103556271  ENAH; enabled homolog (Drosophila) [KO:K05746]
103564050  EVL; Enah/Vasp-like [KO:K23487]
103551082  ACTG1; actin gamma 1 [KO:K05692]
103547895  ACTB; actin beta [KO:K05692]
103550695  ARAP3; ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 3 [KO:K12490]
103553409  RHOA; ras homolog family member A [KO:K04513]
103560907  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103555587  FARP2; FERM, ARH/RhoGEF and pleckstrin domain protein 2 [KO:K06082]
103558482  CDC42; cell division cycle 42 [KO:K04393]
103550104  VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730]
103564042  VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730]
103540380  VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730]
103550555  TIAM1; T-cell lymphoma invasion and metastasis 1 [KO:K05731]
103555589  PARD3; par-3 family cell polarity regulator [KO:K04237]
103542562  PARD6A; par-6 family cell polarity regulator alpha [KO:K06093]
103553166  PARD6G; par-6 family cell polarity regulator gamma [KO:K06093]
103560575  PARD6B; par-6 family cell polarity regulator beta [KO:K06093]
103559872  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
103553747  PRKCI; protein kinase C iota [KO:K06069] [EC:2.7.11.13]
103547082  AFDN; afadin, adherens junction formation factor [KO:K05702]
103558220  CTNND1; catenin delta 1 [KO:K05690]
103549185  KRIT1; KRIT1, ankyrin repeat containing [KO:K17705]
103539969  RGS14; regulator of G-protein signaling 14 [KO:K17706]
103567221  ras association domain-containing protein 5-like [KO:K08015]
103547219  ITGAL; integrin subunit alpha L [KO:K05718]
103547251  ITGAM; integrin subunit alpha M [KO:K06461]
103543384  integrin beta-2-like [KO:K06464]
103565316  ITGB1; integrin subunit beta 1 [KO:K05719]
103555338  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
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]
103563092  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103564566  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103565534  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103563198  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103559485  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103559491  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
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]
103559297  PLCE1; phospholipase C epsilon 1 [KO:K05860] [EC:3.1.4.11]
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]
Compound
C00035  GDP
C00044  GTP
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
Reference
PMID:17182900
  Authors
Kooistra MR, Dube N, Bos JL
  Title
Rap1: a key regulator in cell-cell junction formation.
  Journal
J Cell Sci 120:17-22 (2007)
DOI:10.1242/jcs.03306
Reference
PMID:11331911
  Authors
Bos JL, de Rooij J, Reedquist KA
  Title
Rap1 signalling: adhering to new models.
  Journal
Nat Rev Mol Cell Biol 2:369-77 (2001)
DOI:10.1038/35073073
Reference
PMID:17383543
  Authors
Minato N, Kometani K, Hattori M
  Title
Regulation of immune responses and hematopoiesis by the Rap1 signal.
  Journal
Adv Immunol 93:229-64 (2007)
DOI:10.1016/S0065-2776(06)93006-5
Reference
PMID:15780587
  Authors
Bos JL
  Title
Linking Rap to cell adhesion.
  Journal
Curr Opin Cell Biol 17:123-8 (2005)
DOI:10.1016/j.ceb.2005.02.009
Reference
PMID:12508104
  Authors
Caron E
  Title
Cellular functions of the Rap1 GTP-binding protein: a pattern emerges.
  Journal
J Cell Sci 116:435-40 (2003)
DOI:10.1242/jcs.00238
Reference
PMID:10579920
  Authors
Zwartkruis FJ, Bos JL
  Title
Ras and Rap1: two highly related small GTPases with distinct function.
  Journal
Exp Cell Res 253:157-65 (1999)
DOI:10.1006/excr.1999.4695
Reference
PMID:14607972
  Authors
Hattori M, Minato N
  Title
Rap1 GTPase: functions, regulation, and malignancy.
  Journal
J Biochem 134:479-84 (2003)
DOI:10.1093/jb/mvg180
Reference
PMID:19159611
  Authors
Pannekoek WJ, Kooistra MR, Zwartkruis FJ, Bos JL
  Title
Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors.
  Journal
Biochim Biophys Acta 1788:790-6 (2009)
DOI:10.1016/j.bbamem.2008.12.010
Reference
PMID:19615876
  Authors
Boettner B, Van Aelst L
  Title
Control of cell adhesion dynamics by Rap1 signaling.
  Journal
Curr Opin Cell Biol 21:684-93 (2009)
DOI:10.1016/j.ceb.2009.06.004
Reference
PMID:15803158
  Authors
Xia Z, Storm DR.
  Title
The role of calmodulin as a signal integrator for synaptic plasticity.
  Journal
Nat Rev Neurosci 6:267-76 (2005)
DOI:10.1038/nrn1647
Reference
PMID:17624948
  Authors
Mor A, Dustin ML, Philips MR
  Title
Small GTPases and LFA-1 reciprocally modulate adhesion and signaling.
  Journal
Immunol Rev 218:114-25 (2007)
DOI:10.1111/j.1600-065X.2007.00538.x
Reference
PMID:17624944
  Authors
Burbach BJ, Medeiros RB, Mueller KL, Shimizu Y
  Title
T-cell receptor signaling to integrins.
  Journal
Immunol Rev 218:65-81 (2007)
DOI:10.1111/j.1600-065X.2007.00527.x
Reference
PMID:12765839
  Authors
Stork PJ
  Title
Does Rap1 deserve a bad Rap?
  Journal
Trends Biochem Sci 28:267-75 (2003)
DOI:10.1016/S0968-0004(03)00087-2
Reference
PMID:12351703
  Authors
Banihashemi B, Albert PR
  Title
Dopamine-D2S receptor inhibition of calcium influx, adenylyl cyclase, and mitogen-activated protein kinase in pituitary cells: distinct Galpha and Gbetagamma requirements.
  Journal
Mol Endocrinol 16:2393-404 (2002)
DOI:10.1210/me.2001-0220
Reference
PMID:18363565
  Authors
Banno A, Ginsberg MH
  Title
Integrin activation.
  Journal
Biochem Soc Trans 36:229-34 (2008)
DOI:10.1042/BST0360229
Reference
PMID:19710505
  Authors
Doebele RC, Schulze-Hoepfner FT, Hong J, Chlenski A, Zeitlin BD, Goel K, Gomes S, Liu Y, Abe MK, Nor JE, Lingen MW, Rosner MR
  Title
A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis.
  Journal
Blood 114:4592-600 (2009)
DOI:10.1182/blood-2009-04-217042
Reference
PMID:21402149
  Authors
Breckler M, Berthouze M, Laurent AC, Crozatier B, Morel E, Lezoualc'h F
  Title
Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications.
  Journal
Cell Signal 23:1257-66 (2011)
DOI:10.1016/j.cellsig.2011.03.007
Related
pathway
epz04010  MAPK signaling pathway
epz04014  Ras signaling pathway
epz04020  Calcium signaling pathway
epz04151  PI3K-Akt signaling pathway
epz04510  Focal adhesion
epz04520  Adherens junction
epz04660  T cell receptor signaling pathway
epz04810  Regulation of actin cytoskeleton
KO pathway
ko04015   
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