KEGG   PATHWAY: ko04015Help
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
BRITE hierarchy
Pathway map
ko04015  Rap1 signaling pathway
ko04015

Ortholog table
Disease
H00505  FGFR3-related short limb skeletal dysplasia
H00535  Hereditary lymphedema
H02068  Hypochondroplasia
H02069  SADDAN
Other DBs
BSID: 878042
GO: 0007264
Orthology
K04353  Ras-related protein Rap-1A
K07836  Ras-related protein Rap-1B
K07831  Ras-related protein M-Ras
K08019  Rap guanine nucleotide exchange factor 5
K17697  dedicator of cytokinesis protein 4
K05208  glutamate receptor ionotropic, NMDA 1
K05209  glutamate receptor ionotropic, NMDA 2A
K05210  glutamate receptor ionotropic, NMDA 2B
K02183  calmodulin
K03914  coagulation factor II (thrombin) receptor
K04236  coagulation factor II (thrombin) receptor-like 3
K04270  P2Y purinoceptor 1
K04172  formyl peptide receptor 1
K04289  lysophosphatidic acid receptor 1
K04291  lysophosphatidic acid receptor 2
K04294  lysophosphatidic acid receptor 3
K04275  lysophosphatidic acid receptor 4
K08390  lysophosphatidic acid receptor 5
K04266  adenosine receptor A2a
K04267  adenosine receptor A2b
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:4.6.1.1]
K08042  adenylate cyclase 2 [EC:4.6.1.1]
K08043  adenylate cyclase 3 [EC:4.6.1.1]
K08044  adenylate cyclase 4 [EC:4.6.1.1]
K08045  adenylate cyclase 5 [EC:4.6.1.1]
K08046  adenylate cyclase 6 [EC:4.6.1.1]
K08047  adenylate cyclase 7 [EC:4.6.1.1]
K08048  adenylate cyclase 8 [EC:4.6.1.1]
K08049  adenylate cyclase 9 [EC:4.6.1.1]
K08014  Rap guanine nucleotide exchange factor 3
K04351  Rap guanine nucleotide exchange factor 4
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K05858  phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K12362  RAS guanyl-releasing protein 3
K12361  RAS guanyl-releasing protein 2
K04357  epidermal growth factor
K18496  fibroblast growth factor 1
K18497  fibroblast growth factor 2
K04358  fibroblast growth factor
K22603  fibroblast growth factor 19
K22429  fibroblast growth factor 21
K22428  fibroblast growth factor 23
K05451  nerve growth factor, alpha
K02582  nerve growth factor, beta
K04526  insulin
K05459  insulin-like growth factor 1
K04359  platelet-derived growth factor subunit A
K17386  platelet-derived growth factor subunit B
K05450  platelet derived growth factor C/D
K05453  macrophage colony-stimulating factor 1
K05461  KIT ligand
K05448  vascular endothelial growth factor A
K16858  vascular endothelial growth factor B
K16859  placenta growth factor
K05449  vascular endothelial growth factor C/D
K05460  hepatocyte growth factor
K05465  angiopoietin 1
K05466  angiopoietin 2
K05467  angiopoietin 4
K05462  ephrin-A
K04361  epidermal growth factor receptor [EC:2.7.10.1]
K04362  fibroblast growth factor receptor 1 [EC:2.7.10.1]
K05093  fibroblast growth factor receptor 2 [EC:2.7.10.1]
K05094  fibroblast growth factor receptor 3 [EC:2.7.10.1]
K05095  fibroblast growth factor receptor 4 [EC:2.7.10.1]
K02583  tumor necrosis factor receptor superfamily member 16
K04527  insulin receptor [EC:2.7.10.1]
K05087  insulin-like growth factor 1 receptor [EC:2.7.10.1]
K04363  platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089  platelet-derived growth factor receptor beta [EC:2.7.10.1]
K05090  macrophage colony-stimulating factor 1 receptor [EC:2.7.10.1]
K05091  proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1]
K05096  FMS-like tyrosine kinase 1 [EC:2.7.10.1]
K05097  FMS-like tyrosine kinase 4 [EC:2.7.10.1]
K05098  kinase insert domain protein receptor [EC:2.7.10.1]
K05099  proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1]
K05121  endothelial-specific receptor tyrosine kinase [EC:2.7.10.1]
K05103  Eph receptor A2 [EC:2.7.10.1]
K04438  proto-oncogene C-crk
K06277  Rap guanine nucleotide exchange factor 1
K05726  breast cancer anti-estrogen resistance 1
K05689  cadherin 1, type 1, E-cadherin
K02105  catenin beta 1
K05631  atrophin-1 interacting protein 3 (BAI1-associated protein 1)
K05629  atrophin-1 interacting protein 1
K06112  membrane-associated guanylate kinase-related
K08018  Rap guanine nucleotide exchange factor 2
K08020  Rap guanine nucleotide exchange factor 6
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K07362  linker for activation of T cells
K17698  FYN binding protein
K07361  lymphocyte cytosolic protein 2
K17699  src kinase associated phosphoprotein 1
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K02677  classical protein kinase C alpha type [EC:2.7.11.13]
K19662  classical protein kinase C beta type [EC:2.7.11.13]
K19663  classical protein kinase C gamma type [EC:2.7.11.13]
K06070  protein kinase D [EC:2.7.11.13]
K04145  dopamine receptor D2
K04277  cannabinoid receptor 1
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K04534  guanine nucleotide-binding protein G(o) subunit alpha
K17700  RAP1 GTPase activating protein 1
K17701  signal-induced proliferation-associated 1 like protein 1
K08013  signal-induced proliferation-associated gene 1
K17702  signal-induced proliferation-associated 1 like protein 2
K17703  signal-induced proliferation-associated 1 like protein 3
K04680  DNA-binding protein inhibitor ID1
K16857  thrombospondin 1
K08732  ral guanine nucleotide dissociation stimulator
K07834  Ras-related protein Ral-A
K07835  Ras-related protein Ral-B
K04392  Ras-related C3 botulinum toxin substrate 1
K07860  Ras-related C3 botulinum toxin substrate 2
K07861  Ras-related C3 botulinum toxin substrate 3
K17704  amyloid beta A4 precursor protein-binding family B member 1-interacting protein
K06271  talin
K06476  integrin alpha 2B
K06493  integrin beta 3
K05759  profilin
K06274  vasodilator-stimulated phosphoprotein
K05692  actin beta/gamma 1
K12490  Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3
K04513  Ras homolog gene family, member A
K05704  tyrosine-protein kinase Src [EC:2.7.10.2]
K06082  FERM, RhoGEF and pleckstrin domain protein 2
K04393  cell division control protein 42
K05731  T-lymphoma invasion and metastasis-inducing protein 1
K04237  partitioning defective protein 3
K06093  partitioning defective protein 6
K18952  atypical protein kinase C zeta type [EC:2.7.11.13]
K06069  atypical protein kinase C iota type [EC:2.7.11.13]
K05702  afadin
K05690  catenin (cadherin-associated protein), delta 1
K17705  Krev interaction trapped protein 1
K17706  regulator of G-protein signaling 14
K08015  Ras association domain-containing protein 5
K05718  integrin alpha L
K06461  integrin alpha M
K06464  integrin beta 2
K05719  integrin beta 1
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04432  mitogen-activated protein kinase kinase 3 [EC:2.7.12.2]
K04433  mitogen-activated protein kinase kinase 6 [EC:2.7.12.2]
K04441  p38 MAP kinase [EC:2.7.11.24]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K05860  phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K07829  Ras-related protein R-Ras
Compound
C00035  GDP
C00044  GTP
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Banno A, Ginsberg MH
  Title
Integrin activation.
  Journal
Biochem Soc Trans 36:229-34 (2008)
DOI:10.1042/BST0360229
Reference
  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
  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
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