KEGG   PATHWAY: rno04015
rno04015                    Pathway                                

Rap1 signaling pathway - Rattus norvegicus (rat)
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.
Environmental Information Processing; Signal transduction
Pathway map
rno04015  Rap1 signaling pathway

Other DBs
GO: 0007264
Rattus norvegicus (rat) [GN:rno]
295347  Rap1a; ras-related protein Rap-1A [KO:K04353]
171337  Rap1b; ras-related protein Rap-1b [KO:K07836]
25482  Mras; ras-related protein M-Ras [KO:K07831]
362799  Rapgef5; rap guanine nucleotide exchange factor 5 [KO:K08019]
366608  Dock4; dedicator of cytokinesis protein 4 isoform X1 [KO:K17697]
24408  Grin1; glutamate receptor ionotropic, NMDA 1 isoform 1a precursor [KO:K05208]
24409  Grin2a; glutamate receptor ionotropic, NMDA 2A precursor [KO:K05209]
24410  Grin2b; glutamate receptor ionotropic, NMDA 2B precursor [KO:K05210]
50663  Calm2; calmodulin-2 [KO:K02183]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
25439  F2r; proteinase-activated receptor 1 precursor [KO:K03914]
116498  F2rl3; proteinase-activated receptor 4 [KO:K04236]
25265  P2ry1; P2Y purinoceptor 1 [KO:K04270]
292409  Fpr1; fMet-Leu-Phe receptor [KO:K04172]
116744  Lpar1; lysophosphatidic acid receptor 1 [KO:K04289]
498609  Lpar2; lysophosphatidic acid receptor 2 [KO:K04291]
66025  Lpar3; lysophosphatidic acid receptor 3 [KO:K04294]
302378  Lpar4; lysophosphatidic acid receptor 4 [KO:K04275]
500317  Lpar5; lysophosphatidic acid receptor 5 [KO:K08390]
25369  Adora2a; adenosine receptor A2a A2AR [KO:K04266]
29316  Adora2b; adenosine receptor A2b [KO:K04267]
24896  Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:]
59326  Rapgef3; rap guanine nucleotide exchange factor 3 [KO:K08014]
252857  Rapgef4; rap guanine nucleotide exchange factor 4 [KO:K04351]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:]
313874  Rasgrp3; ras guanyl-releasing protein 3 [KO:K12362]
361714  Rasgrp2; RAS guanyl-releasing protein 2 [KO:K12361]
25313  Egf; pro-epidermal growth factor precursor [KO:K04357]
25317  Fgf1; fibroblast growth factor 1 [KO:K18496]
54250  Fgf2; fibroblast growth factor 2 [KO:K18497]
170633  Fgf3; fibroblast growth factor 3 precursor [KO:K04358]
116499  Fgf4; fibroblast growth factor 4 precursor [KO:K04358]
60662  Fgf5; fibroblast growth factor 5 precursor [KO:K04358]
170700  Fgf6; fibroblast growth factor 6 [KO:K04358]
29348  Fgf7; fibroblast growth factor 7 precursor [KO:K04358]
29349  Fgf8; fibroblast growth factor 8 precursor [KO:K04358]
25444  Fgf9; fibroblast growth factor 9 [KO:K04358]
25443  Fgf10; fibroblast growth factor 10 precursor [KO:K04358]
60464  Fgf16; fibroblast growth factor 16 [KO:K04358]
29368  Fgf17; fibroblast growth factor 17 precursor [KO:K04358]
29369  Fgf18; fibroblast growth factor 18 precursor [KO:K04358]
66017  Fgf20; fibroblast growth factor 20 [KO:K04358]
170579  Fgf22; fibroblast growth factor 22 precursor [KO:K04358]
170582  Fgf19; fibroblast growth factor 19 precursor [KO:K22603]
170580  Fgf21; fibroblast growth factor 21 precursor [KO:K22429]
170583  Fgf23; fibroblast growth factor 23 precursor [KO:K22428]
310738  Ngf; beta-nerve growth factor precursor [KO:K02582]
24506  Ins2; insulin-2 preproprotein [KO:K04526]
24505  Ins1; insulin-1 preproprotein [KO:K04526]
24482  Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459]
25266  Pdgfa; platelet-derived growth factor subunit A precursor [KO:K04359]
24628  Pdgfb; platelet-derived growth factor subunit B precursor [KO:K17386]
79429  Pdgfc; platelet-derived growth factor C precursor [KO:K05450]
66018  Pdgfd; platelet-derived growth factor D precursor [KO:K05450]
78965  Csf1; macrophage colony-stimulating factor 1 precursor [KO:K05453]
60427  Kitlg; kit ligand isoform 1 precursor [KO:K05461]
83785  Vegfa; vascular endothelial growth factor A isoform 6 precursor [KO:K05448]
89811  Vegfb; vascular endothelial growth factor B precursor [KO:K16858]
94203  Pgf; placenta growth factor precursor [KO:K16859]
114111  Vegfc; vascular endothelial growth factor C precursor [KO:K05449]
360457  Vegfd; vascular endothelial growth factor D precursor [KO:K05449]
24446  Hgf; hepatocyte growth factor preproprotein [KO:K05460]
89807  Angpt1; angiopoietin-1 precursor [KO:K05465]
89805  Angpt2; angiopoietin-2 precursor [KO:K05466]
296269  Angpt4; angiopoietin-4 precursor [KO:K05467]
94268  Efna1; ephrin-A1 precursor [KO:K05462]
116683  Efna5; ephrin-A5 precursor [KO:K05462]
310643  Efna4; ephrin-A4 precursor [KO:K05462]
84358  Efna2; ephrin-A2 precursor [KO:K05462]
170901  Efna3; ephrin-A3 isoform X1 [KO:K05462]
24329  Egfr; epidermal growth factor receptor precursor [KO:K04361] [EC:]
79114  Fgfr1; fibroblast growth factor receptor 1 precursor [KO:K04362] [EC:]
25022  Fgfr2; fibroblast growth factor receptor 2 isoform b [KO:K05093] [EC:]
84489  Fgfr3; fibroblast growth factor receptor 3 precursor [KO:K05094] [EC:]
25114  Fgfr4; fibroblast growth factor receptor 4 precursor [KO:K05095] [EC:]
24596  Ngfr; tumor necrosis factor receptor superfamily member 16 precursor [KO:K02583]
24954  Insr; insulin receptor preproprotein [KO:K04527] [EC:]
25718  Igf1r; insulin-like growth factor 1 receptor precursor [KO:K05087] [EC:]
25267  Pdgfra; platelet-derived growth factor receptor alpha precursor [KO:K04363] [EC:]
24629  Pdgfrb; platelet-derived growth factor receptor beta precursor [KO:K05089] [EC:]
307403  Csf1r; macrophage colony-stimulating factor 1 receptor precursor [KO:K05090] [EC:]
64030  Kit; mast/stem cell growth factor receptor Kit precursor [KO:K05091] [EC:]
54251  Flt1; vascular endothelial growth factor receptor 1 isoform 2 precursor [KO:K05096] [EC:]
114110  Flt4; vascular endothelial growth factor receptor 3 precursor [KO:K05097] [EC:]
25589  Kdr; vascular endothelial growth factor receptor 2 precursor [KO:K05098] [EC:]
24553  Met; hepatocyte growth factor receptor precursor [KO:K05099] [EC:]
89804  Tek; angiopoietin-1 receptor [KO:K05121] [EC:]
366492  Epha2; ephrin type-A receptor 2 precursor [KO:K05103] [EC:]
54245  Crk; adapter molecule crk [KO:K04438]
287942  Crkl; crk-like protein [KO:K04438]
63881  Rapgef1; rap guanine nucleotide exchange factor 1 isoform X19 [KO:K06277]
25414  Bcar1; breast cancer anti-estrogen resistance protein 1 [KO:K05726]
83502  Cdh1; cadherin-1 precursor [KO:K05689]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
500261  Magi1; membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 [KO:K05631]
113970  Magi2; membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 [KO:K05629]
245903  Magi3; membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3 [KO:K06112]
310533  Rapgef2; rap guanine nucleotide exchange factor 2 [KO:K08018]
303141  Rapgef6; rap guanine nucleotide exchange factor 6 [KO:K08020]
81511  Lat; linker for activation of T-cells family member 1 [KO:K07362]
499537  Fyb1; FYN-binding protein 1 [KO:K17698]
155918  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
286975  Skap1; src kinase-associated phosphoprotein 1 [KO:K17699]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:]
85421  Prkd1; serine/threonine-protein kinase D1 [KO:K06070] [EC:]
292658  Prkd2; serine/threonine-protein kinase D2 [KO:K06070] [EC:]
313834  Prkd3; serine/threonine-protein kinase D3 [KO:K06070] [EC:]
24318  Drd2; D(2) dopamine receptor [KO:K04145]
25248  Cnr1; cannabinoid receptor 1 [KO:K04277]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
50664  Gnao1; guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
313644  Rap1gap; rap1 GTPase-activating protein 1 [KO:K17700]
246212  Sipa1l1; signal-induced proliferation-associated 1-like protein 1 isoform 1 [KO:K17701]
361710  Sipa1; signal-induced proliferation-associated protein 1 [KO:K08013]
361442  Sipa1l2; signal-induced proliferation-associated 1-like protein 2 [KO:K17702]
25261  Id1; DNA-binding protein inhibitor ID-1 [KO:K04680]
445442  Thbs1; thrombospondin-1 precursor [KO:K16857]
29622  Ralgds; ral guanine nucleotide dissociation stimulator [KO:K08732]
81757  Rala; ras-related protein Ral-A [KO:K07834]
116546  Ralb; ras-related protein Ral-B [KO:K07835]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
366957  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
307171  Apbb1ip; amyloid beta A4 precursor protein-binding family B member 1-interacting protein [KO:K17704]
315776  Tln2; talin-2 isoform X1 [KO:K06271]
313494  Tln1; talin-1 [KO:K06271]
685269  Itga2b; integrin alpha-IIb [KO:K06476]
29302  Itgb3; integrin beta-3 precursor [KO:K06493]
171436  Mk1; Mk1 protein [KO:K05759]
64303  Pfn1; profilin-1 [KO:K05759]
81531  Pfn2; profilin-2 [KO:K05759]
685936  Pfn3; profilin-3 [KO:K05759]
494222  Pfn4; profilin-4 [KO:K05759]
102551431  profilin-2-like [KO:K05759]
361517  Vasp; vasodilator-stimulated phosphoprotein [KO:K06274]
360891  Enah; protein enabled homolog [KO:K05746]
79115  Evl; ena/VASP-like protein [KO:K23487]
100361457  actin, cytoplasmic 2 [KO:K05692]
81822  Actb; actin, cytoplasmic 1 [KO:K05692]
287876  Actg1; actin, cytoplasmic 2 [KO:K05692]
361314  Arap3; arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 3 isoform X4 [KO:K12490]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
316639  Farp2; FERM, RhoGEF and pleckstrin domain-containing protein 2 [KO:K06082]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
25156  Vav1; proto-oncogene vav [KO:K05730]
295378  Vav3; guanine nucleotide exchange factor VAV3 [KO:K05730]
296603  Vav2; guanine nucleotide exchange factor VAV2 [KO:K05730]
304109  Tiam1; T-lymphoma invasion and metastasis-inducing protein 1 [KO:K05731]
81918  Pard3; partitioning defective 3 homolog [KO:K04237]
307237  Pard6g; partitioning defective 6 homolog gamma [KO:K06093]
307799  Pard6a; partitioning defective 6 homolog alpha isoform 1 [KO:K06093]
362279  Pard6b; partitioning defective 6 homolog beta [KO:K06093]
25522  Prkcz; protein kinase C zeta type [KO:K18952] [EC:]
84006  Prkci; protein kinase C iota type [KO:K06069] [EC:]
26955  Afdn; afadin [KO:K05702]
311163  Ctnnd1; catenin delta-1 [KO:K05690]
362317  Krit1; krev interaction trapped protein 1 [KO:K17705]
114705  Rgs14; regulator of G-protein signaling 14 [KO:K17706]
54355  Rassf5; ras association domain-containing protein 5 [KO:K08015]
308995  Itgal; integrin alpha-L precursor [KO:K05718]
25021  Itgam; integrin alpha-M precursor [KO:K06461]
309684  Itgb2; integrin beta-2 precursor [KO:K06464]
24511  Itgb1; integrin beta-1 precursor [KO:K05719]
114486  Braf; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
303200  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:]
114495  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
114633  Plce1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 [KO:K05860] [EC:]
293621  Hras; GTPase HRas [KO:K02833]
367858  GTPase HRas [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
361568  Rras; ras-related protein R-Ras [KO:K07829]
C00035  GDP
C00044  GTP
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
Kooistra MR, Dube N, Bos JL
Rap1: a key regulator in cell-cell junction formation.
J Cell Sci 120:17-22 (2007)
Bos JL, de Rooij J, Reedquist KA
Rap1 signalling: adhering to new models.
Nat Rev Mol Cell Biol 2:369-77 (2001)
Minato N, Kometani K, Hattori M
Regulation of immune responses and hematopoiesis by the Rap1 signal.
Adv Immunol 93:229-64 (2007)
Bos JL
Linking Rap to cell adhesion.
Curr Opin Cell Biol 17:123-8 (2005)
Caron E
Cellular functions of the Rap1 GTP-binding protein: a pattern emerges.
J Cell Sci 116:435-40 (2003)
Zwartkruis FJ, Bos JL
Ras and Rap1: two highly related small GTPases with distinct function.
Exp Cell Res 253:157-65 (1999)
Hattori M, Minato N
Rap1 GTPase: functions, regulation, and malignancy.
J Biochem 134:479-84 (2003)
Pannekoek WJ, Kooistra MR, Zwartkruis FJ, Bos JL
Cell-cell junction formation: the role of Rap1 and Rap1 guanine nucleotide exchange factors.
Biochim Biophys Acta 1788:790-6 (2009)
Boettner B, Van Aelst L
Control of cell adhesion dynamics by Rap1 signaling.
Curr Opin Cell Biol 21:684-93 (2009)
Xia Z, Storm DR.
The role of calmodulin as a signal integrator for synaptic plasticity.
Nat Rev Neurosci 6:267-76 (2005)
Mor A, Dustin ML, Philips MR
Small GTPases and LFA-1 reciprocally modulate adhesion and signaling.
Immunol Rev 218:114-25 (2007)
Burbach BJ, Medeiros RB, Mueller KL, Shimizu Y
T-cell receptor signaling to integrins.
Immunol Rev 218:65-81 (2007)
Stork PJ
Does Rap1 deserve a bad Rap?
Trends Biochem Sci 28:267-75 (2003)
Banihashemi B, Albert PR
Dopamine-D2S receptor inhibition of calcium influx, adenylyl cyclase, and mitogen-activated protein kinase in pituitary cells: distinct Galpha and Gbetagamma requirements.
Mol Endocrinol 16:2393-404 (2002)
Banno A, Ginsberg MH
Integrin activation.
Biochem Soc Trans 36:229-34 (2008)
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
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.
Blood 114:4592-600 (2009)
Breckler M, Berthouze M, Laurent AC, Crozatier B, Morel E, Lezoualc'h F
Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications.
Cell Signal 23:1257-66 (2011)
rno04010  MAPK signaling pathway
rno04014  Ras signaling pathway
rno04020  Calcium signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04510  Focal adhesion
rno04520  Adherens junction
rno04660  T cell receptor signaling pathway
rno04810  Regulation of actin cytoskeleton
KO pathway

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