KEGG   PATHWAY: ko04015
Entry
ko04015                     Pathway                                
Name
Rap1 signaling pathway
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
ko04015  Rap1 signaling pathway
ko04015

Other DBs
GO: 0007264
Orthology
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K02105  CTNNB1; catenin beta 1
K02183  CALM; calmodulin
K02582  NGFB; nerve growth factor, beta
K02583  NGFR, TNFRSF16, CD271; tumor necrosis factor receptor superfamily member 16
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K02833  HRAS; GTPase HRas
K03914  F2R, PAR1; coagulation factor II (thrombin) receptor
K04145  DRD2; dopamine receptor D2
K04172  FPR1; formyl peptide receptor 1
K04236  F2RL3, PAR4; coagulation factor II (thrombin) receptor-like 3
K04237  PARD3; partitioning defective protein 3
K04266  ADORA2A, ADOR; adenosine receptor A2a
K04267  ADORA2B; adenosine receptor A2b
K04270  P2RY1; P2Y purinoceptor 1
K04275  LPAR4, GPR23; lysophosphatidic acid receptor 4
K04277  CNR1; cannabinoid receptor 1
K04289  LPAR1, EDG2; lysophosphatidic acid receptor 1
K04291  LPAR2, EDG4; lysophosphatidic acid receptor 2
K04294  LPAR3, EDG7; lysophosphatidic acid receptor 3
K04351  RAPGEF4, EPAC2; Rap guanine nucleotide exchange factor 4
K04353  RAP1A; Ras-related protein Rap-1A
K04357  EGF; epidermal growth factor
K04358  FGF; fibroblast growth factor
K04359  PDGFA; platelet-derived growth factor subunit A
K04361  EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]
K04362  FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1]
K04363  PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04432  MAP2K3, MKK3; mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04438  CRK, CRKII; C-crk adapter molecule crk
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04513  RHOA; Ras homolog gene family, member A
K04526  INS; insulin
K04527  INSR, CD220; insulin receptor [EC:2.7.10.1]
K04534  GNAO, G-ALPHA-O; guanine nucleotide-binding protein G(o) subunit alpha
K04630  GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04632  GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04680  ID1; DNA-binding protein inhibitor ID1
K05087  IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1]
K05089  PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1]
K05090  CSF1R, FMS, CD115; macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1]
K05091  KIT, SCFR, CD117; proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1]
K05093  FGFR2, CD332; fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094  FGFR3, CD333; fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095  FGFR4, CD334; fibroblast growth factor receptor 4 [EC:2.7.10.1]
K05096  FLT1, VEGFR1; FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05097  FLT4, VEGFR3; FMS-like tyrosine kinase 4 [EC:2.7.10.1]
K05098  KDR, VEGFR2, CD309; kinase insert domain protein receptor [EC:2.7.10.1]
K05099  MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05103  EPHA2, ECK; Eph receptor A2 [EC:2.7.10.1]
K05121  TEK, TIE2, CD202; endothelial-specific receptor tyrosine kinase [EC:2.7.10.1]
K05208  GRIN1; glutamate receptor ionotropic, NMDA 1
K05209  GRIN2A; glutamate receptor ionotropic, NMDA 2A
K05210  GRIN2B; glutamate receptor ionotropic, NMDA 2B
K05448  VEGFA; vascular endothelial growth factor A
K05449  VEGFC_D; vascular endothelial growth factor C/D
K05450  PDGFC_D; platelet derived growth factor C/D
K05451  NGFA; nerve growth factor, alpha
K05453  CSF1, MCSF; macrophage colony-stimulating factor 1
K05459  IGF1; insulin-like growth factor 1
K05460  HGF; hepatocyte growth factor
K05461  KITLG; KIT ligand
K05462  EFNA; ephrin-A
K05465  ANGPT1; angiopoietin 1
K05466  ANGPT2; angiopoietin 2
K05467  ANGPT4; angiopoietin 4
K05629  AIP1; atrophin-1 interacting protein 1
K05631  AIP3, WWP3, BAIAP1; atrophin-1 interacting protein 3 (BAI1-associated protein 1)
K05689  CDH1, CDHE, CD324; cadherin 1, type 1, E-cadherin
K05690  CTNND1; catenin (cadherin-associated protein), delta 1
K05692  ACTB_G1; actin beta/gamma 1
K05702  AF6, MLLT4; afadin
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05718  ITGAL, CD11a; integrin alpha L
K05719  ITGB1, CD29; integrin beta 1
K05726  BCAR1, CAS; breast cancer anti-estrogen resistance 1
K05730  VAV; guanine nucleotide exchange factor VAV
K05731  TIAM1; T-lymphoma invasion and metastasis-inducing protein 1
K05746  ENAH, MENA; enabled
K05759  PFN; profilin
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05860  PLCE; phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]
K06069  PRKCI; atypical protein kinase C iota type [EC:2.7.11.13]
K06070  PKD; protein kinase D [EC:2.7.11.13]
K06082  FARP2, FRG; FERM, RhoGEF and pleckstrin domain protein 2
K06093  PARD6; partitioning defective protein 6
K06112  MAGI3; membrane-associated guanylate kinase-related
K06271  TLN; talin
K06274  VASP; vasodilator-stimulated phosphoprotein
K06277  RAPGEF1, GRF2; Rap guanine nucleotide exchange factor 1
K06461  ITGAM, CD11b; integrin alpha M
K06464  ITGB2, CD18; integrin beta 2
K06476  ITGA2B, CD41; integrin alpha 2B
K06493  ITGB3, CD61; integrin beta 3
K07361  LCP2; lymphocyte cytosolic protein 2
K07362  LAT; linker for activation of T cells family member 1
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07829  RRAS; Ras-related protein R-Ras
K07831  MRAS; Ras-related protein M-Ras
K07834  RALA; Ras-related protein Ral-A
K07835  RALB; Ras-related protein Ral-B
K07836  RAP1B; Ras-related protein Rap-1B
K07860  RAC2; Ras-related C3 botulinum toxin substrate 2
K07861  RAC3; Ras-related C3 botulinum toxin substrate 3
K08013  SIPA1; signal-induced proliferation-associated gene 1
K08014  RAPGEF3, EPAC1; Rap guanine nucleotide exchange factor 3
K08015  RASSF5, RAPL; Ras association domain-containing protein 5
K08018  RAPGEF2, PDZGEF1; Rap guanine nucleotide exchange factor 2
K08019  RAPGEF5; Rap guanine nucleotide exchange factor 5
K08020  RAPGEF6, PDZGEF2; Rap guanine nucleotide exchange factor 6
K08041  ADCY1; adenylate cyclase 1 [EC:4.6.1.1]
K08042  ADCY2; adenylate cyclase 2 [EC:4.6.1.1]
K08043  ADCY3; adenylate cyclase 3 [EC:4.6.1.1]
K08044  ADCY4; adenylate cyclase 4 [EC:4.6.1.1]
K08045  ADCY5; adenylate cyclase 5 [EC:4.6.1.1]
K08046  ADCY6; adenylate cyclase 6 [EC:4.6.1.1]
K08047  ADCY7; adenylate cyclase 7 [EC:4.6.1.1]
K08048  ADCY8; adenylate cyclase 8 [EC:4.6.1.1]
K08049  ADCY9; adenylate cyclase 9 [EC:4.6.1.1]
K08390  LPAR5, GPR92; lysophosphatidic acid receptor 5
K08732  RALGDS; ral guanine nucleotide dissociation stimulator
K10784  TRAV; T cell receptor alpha chain V region
K10785  TRBV; T-cell receptor beta chain V region
K12361  RASGRP2; RAS guanyl-releasing protein 2
K12362  RASGRP3; RAS guanyl-releasing protein 3
K12490  ARAP3; Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3
K16857  THBS1; thrombospondin 1
K16858  VEGFB; vascular endothelial growth factor B
K16859  PGF; placenta growth factor
K17386  PDGFB; platelet-derived growth factor subunit B
K17697  DOCK4; dedicator of cytokinesis protein 4
K17698  FYB, ADAP; FYN binding protein
K17699  SKAP1, SKAP55; src kinase associated phosphoprotein 1
K17700  RAP1GAP, RAPGAP; RAP1 GTPase activating protein 1
K17701  SIPA1L1, E6TP1; signal-induced proliferation-associated 1 like protein 1
K17702  SIPA1L2, SPAL2; signal-induced proliferation-associated 1 like protein 2
K17703  SIPA1L3, SPAL3; signal-induced proliferation-associated 1 like protein 3
K17704  APBB1IP, RIAM; amyloid beta A4 precursor protein-binding family B member 1-interacting protein
K17705  KRIT1, CCM1; Krev interaction trapped protein 1
K17706  RGS14; regulator of G-protein signaling 14
K18496  FGF1; fibroblast growth factor 1
K18497  FGF2; fibroblast growth factor 2
K18952  PRKCZ; atypical protein kinase C zeta type [EC:2.7.11.13]
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K22428  FGF23; fibroblast growth factor 23
K22429  FGF21; fibroblast growth factor 21
K22603  FGF19; fibroblast growth factor 19
K23487  EVL; Ena/VASP-like protein
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
ko04010  MAPK signaling pathway
ko04014  Ras signaling pathway
ko04020  Calcium signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04510  Focal adhesion
ko04520  Adherens junction
ko04660  T cell receptor signaling pathway
ko04810  Regulation of actin cytoskeleton

DBGET integrated database retrieval system