KEGG   PATHWAY: hsa04540
Entry
hsa04540                    Pathway                                
Name
Gap junction - Homo sapiens (human)
Description
Gap junctions contain intercellular channels that allow direct communication between the cytosolic compartments of adjacent cells. Each gap junction channel is formed by docking of two 'hemichannels', each containing six connexins, contributed by each neighboring cell. These channels permit the direct transfer of small molecules including ions, amino acids, nucleotides, second messengers and other metabolites between adjacent cells. Gap junctional communication is essential for many physiological events, including embryonic development, electrical coupling, metabolic transport, apoptosis, and tissue homeostasis. Communication through Gap Junction is sensitive to a variety of stimuli, including changes in the level of intracellular Ca2+, pH, transjunctional applied voltage and phosphorylation/dephosphorylation processes. This figure represents the possible activation routes of different protein kinases involved in Cx43 and Cx36 phosphorylation.
Class
Cellular Processes; Cellular community - eukaryotes
Pathway map
hsa04540  Gap junction
hsa04540

Drug
D00491  Paclitaxel (JAN/USP/INN)
D00570  Colchicine (JP19/USP)
D00599  Carteolol hydrochloride (JP19/USP)
D01068  Vinblastine sulfate (JP19/USP)
D01105  Moperone hydrochloride (JAN)
D01769  Vindesine sulfate (JAN/USAN)
D01919  Soblidotin (JAN/INN)
D01935  Vinorelbine tartrate (USP)
D02035  Timiperone (JAN)
D02165  Docetaxel (USP)
D02197  Vincristine sulfate (JP19/USP)
D02371  Clocapramine hydrochloride hydrate (JP19)
D02372  Perospirone hydrochloride hydrate (JP19)
D02605  Methoxypromazine maleate
D02623  Moperone (INN)
D02641  Butaclamol hydrochloride (USAN)
D02670  Mazapertine succinate (USAN)
D02681  Piquindone hydrochloride (USAN)
D02682  Remoxipride (USAN)
D02683  Remoxipride hydrochloride (USAN)
D03059  Batabulin sodium (USAN)
D03065  Becaplermin (USAN/INN)
D03364  Cantuzumab mertansine (USAN)
D04645  Ixabepilone (JAN/USAN/INN)
D04864  Maytansine (USAN)
D05062  Mivobulin isethionate (USAN)
D05333  Paclitaxel poliglumex (USAN/INN)
D06001  Taltobulin (USAN/INN)
D06009  Tasidotin hydrochloride (USAN)
D06304  Vindesine (USAN/INN)
D06305  Vinepidine sulfate (USAN)
D06306  Vinglycinate sulfate (USAN)
D06307  Vinleurosine sulfate (USAN)
D06308  Vinrosidine sulfate (USAN)
D06309  Vinzolidine sulfate (USAN)
D06560  Batabulin (USAN/INN)
D06576  Cevipabulin fumarate (USAN)
D07624  Carteolol (INN)
D07718  Clocapramine (INN)
D07866  Docetaxel (JAN/INN)
D08675  Vinblastine (INN)
D08679  Vincristine (INN)
D08680  Vinorelbine (INN)
D08889  Cevipabulin succinate (USAN)
D08914  Eribulin mesylate (USAN)
D09032  Vinflunine ditartrate (USAN)
D09755  Cabazitaxel (USAN/INN)
D09927  Lorvotuzumab mertansine (USAN/INN)
D10029  Verubulin (USAN/INN)
D10030  Verubulin hydrochloride (USAN)
D10452  Cabazitaxel acetonate (JAN)
D10454  Cantuzumab ravtansine (USAN/INN)
D11228  Soravtansine (USAN)
D11238  Lifastuzumab vedotin (USAN/INN)
D11494  Lisavanbulin (USAN/INN)
D11525  Enfortumab vedotin (USAN)
D11681  Avanbulin (USAN/INN)
D11691  Tirbanibulin (JAN/USAN/INN)
D11692  Tirbanibulin mesylate (USAN)
D11814  Tisotumab vedotin (USAN/INN)
D12183  Farletuzumab ecteribulin (USAN)
D12516  Zagociguat (USAN/INN)
D12519  Sabizabulin (USAN/INN)
D12520  Sabizabulin hydrochloride (USAN)
D12642  Fipaxalparant (USAN/INN)
D12657  Admilparant (JAN/USAN)
D12881  Psilocybin (USAN)
D13035  Bexicaserin (USAN/INN)
D13036  Bexicaserin hydrochloride (USAN)
Other DBs
GO: 0005921
Organism
Homo sapiens (human) [GN:hsa]
Gene
10376  TUBA1B; tubulin alpha-1B chain [KO:K07374]
10381  TUBB3; tubulin beta-3 chain isoform 1 [KO:K07375]
10382  TUBB4A; tubulin beta-4A chain isoform 3 [KO:K07375]
10383  TUBB4B; tubulin beta-4B chain [KO:K07375]
107  ADCY1; adenylate cyclase type 1 isoform 1 [KO:K08041] [EC:4.6.1.1]
10746  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
108  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
109  ADCY3; adenylate cyclase type 3 isoform 2 [KO:K08043] [EC:4.6.1.1]
111  ADCY5; adenylate cyclase type 5 isoform 1 [KO:K08045] [EC:4.6.1.1]
112  ADCY6; adenylate cyclase type 6 isoform 1 [KO:K08046] [EC:4.6.1.1]
112714  TUBA3E; tubulin alpha-3E chain [KO:K07374]
113  ADCY7; adenylate cyclase type 7 isoform 1 [KO:K08047] [EC:4.6.1.1]
113457  TUBA3D; tubulin alpha-3D chain [KO:K07374]
114  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
115  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
1453  CSNK1D; casein kinase I isoform delta isoform 1 [KO:K08959] [EC:2.7.11.1]
153  ADRB1; beta-1 adrenergic receptor [KO:K04141]
1812  DRD1; D(1A) dopamine receptor [KO:K04144]
1813  DRD2; D(2) dopamine receptor isoform long [KO:K04145]
1902  LPAR1; lysophosphatidic acid receptor 1 isoform a [KO:K04289]
1950  EGF; pro-epidermal growth factor isoform 1 preproprotein [KO:K04357]
1956  EGFR; epidermal growth factor receptor isoform a precursor [KO:K04361] [EC:2.7.10.1]
196883  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
203068  TUBB; tubulin beta chain isoform b [KO:K07375]
23236  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform a [KO:K05858] [EC:3.1.4.11]
260334  TUBB8B; tubulin beta 8B isoform 1 [KO:K07375]
2697  GJA1; gap junction alpha-1 protein [KO:K07372]
2767  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
2770  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform 1 [KO:K04630]
2771  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 1 [KO:K04630]
2773  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
2776  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
2778  GNAS; protein GNAS isoform XLas [KO:K04632]
2885  GRB2; growth factor receptor-bound protein 2 isoform 1 [KO:K04364]
2911  GRM1; metabotropic glutamate receptor 1 isoform alpha precursor [KO:K04603]
2915  GRM5; metabotropic glutamate receptor 5 isoform a precursor [KO:K04604]
2977  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform 2 [KO:K12318] [EC:4.6.1.2]
2982  GUCY1A1; guanylate cyclase soluble subunit alpha-1 isoform A [KO:K12318] [EC:4.6.1.2]
2983  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform 2 [KO:K12319] [EC:4.6.1.2]
3265  HRAS; GTPase HRas isoform 1 [KO:K02833]
3356  HTR2A; 5-hydroxytryptamine receptor 2A isoform 1 [KO:K04157]
3357  HTR2B; 5-hydroxytryptamine receptor 2B isoform 1 [KO:K04157]
3358  HTR2C; 5-hydroxytryptamine receptor 2C isoform a precursor [KO:K04157]
347688  TUBB8; tubulin beta-8 chain isoform 1 [KO:K07375]
347733  TUBB2B; tubulin beta-2B chain [KO:K07375]
3708  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform 4 [KO:K04958]
3709  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform 1 [KO:K04959]
3710  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 [KO:K04960]
3845  KRAS; GTPase KRas isoform a [KO:K07827]
4893  NRAS; GTPase NRas [KO:K07828]
5154  PDGFA; platelet-derived growth factor subunit A isoform 1 preproprotein [KO:K04359]
5155  PDGFB; platelet-derived growth factor subunit B isoform 1 preproprotein [KO:K17386]
5156  PDGFRA; platelet-derived growth factor receptor alpha isoform 1 precursor [KO:K04363] [EC:2.7.10.1]
5159  PDGFRB; platelet-derived growth factor receptor beta isoform 1 precursor [KO:K05089] [EC:2.7.10.1]
51807  TUBA8; tubulin alpha-8 chain isoform 1 [KO:K07374]
5330  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform 1 [KO:K05858] [EC:3.1.4.11]
5331  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform 1 [KO:K05858] [EC:3.1.4.11]
5332  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform b [KO:K05858] [EC:3.1.4.11]
5566  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform Calpha1 [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform 2 [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
5578  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
5579  PRKCB; protein kinase C beta type isoform 1 [KO:K19662] [EC:2.7.11.13]
5582  PRKCG; protein kinase C gamma type isoform 2 [KO:K19663] [EC:2.7.11.13]
5592  PRKG1; cGMP-dependent protein kinase 1 isoform 1 [KO:K07376] [EC:2.7.11.12]
5593  PRKG2; cGMP-dependent protein kinase 2 isoform a [KO:K19477] [EC:2.7.11.12]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 isoform 1 [KO:K04371] [EC:2.7.11.24]
5598  MAPK7; mitogen-activated protein kinase 7 isoform 1 [KO:K04464] [EC:2.7.11.24]
56034  PDGFC; platelet-derived growth factor C precursor [KO:K05450]
5604  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform 1 [KO:K04369] [EC:2.7.12.2]
5607  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform A [KO:K04463] [EC:2.7.12.2]
57369  GJD2; gap junction delta-2 protein [KO:K07373]
5894  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366] [EC:2.7.11.1]
6654  SOS1; son of sevenless homolog 1 isoform 1 [KO:K03099]
6655  SOS2; son of sevenless homolog 2 isoform 1 [KO:K03099]
6714  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
7082  TJP1; tight junction protein 1 isoform a [KO:K05701]
7277  TUBA4A; tubulin alpha-4A chain isoform 1 [KO:K07374]
7278  TUBA3C; tubulin alpha-3C chain [KO:K07374]
7280  TUBB2A; tubulin beta-2A chain isoform 1 [KO:K07375]
7846  TUBA1A; tubulin alpha-1A chain isoform 1 [KO:K07374]
79861  TUBAL3; tubulin alpha chain-like 3 isoform 1 [KO:K07374]
80310  PDGFD; platelet-derived growth factor D isoform 1 precursor [KO:K05450]
81027  TUBB1; tubulin beta-1 chain [KO:K07375]
84617  TUBB6; tubulin beta-6 chain isoform 1 [KO:K07375]
84790  TUBA1C; tubulin alpha-1C chain isoform c [KO:K07374]
983  CDK1; cyclin-dependent kinase 1 isoform 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00165  Diacylglycerol
C00533  Nitric oxide
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00681  1-Acyl-sn-glycerol 3-phosphate
C00780  Serotonin
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C03758  Dopamine
Reference
PMID:14506308
  Authors
Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC.
  Title
Plasma membrane channels formed by connexins: their regulation and functions.
  Journal
Physiol Rev 83:1359-400 (2003)
DOI:10.1152/physrev.00007.2003
Reference
PMID:15033580
  Authors
Warn-Cramer BJ, Lau AF.
  Title
Regulation of gap junctions by tyrosine protein kinases.
  Journal
Biochim Biophys Acta 1662:81-95 (2004)
DOI:10.1016/j.bbamem.2003.10.018
Reference
PMID:9535909
  Authors
Warn-Cramer BJ, Cottrell GT, Burt JM, Lau AF.
  Title
Regulation of connexin-43 gap junctional intercellular communication by mitogen-activated protein kinase.
  Journal
J Biol Chem 273:9188-96 (1998)
DOI:10.1074/jbc.273.15.9188
Reference
PMID:10751659
  Authors
Roerig B, Feller MB.
  Title
Neurotransmitters and gap junctions in developing neural circuits.
  Journal
Brain Res Brain Res Rev 32:86-114 (2000)
DOI:10.1016/S0165-0173(99)00069-7
Reference
PMID:10873290
  Authors
Hatton GI.
  Title
Synaptic modulation of neuronal coupling.
  Journal
Cell Biol Int 22:765-80 (1998)
DOI:10.1006/cbir.1998.0386
Reference
PMID:12566218
  Authors
Cruciani V, Mikalsen SO.
  Title
Connexins, gap junctional intercellular communication and kinases.
  Journal
Biol Cell 94:433-43 (2002)
DOI:10.1016/S0248-4900(02)00014-X
Reference
PMID:15094344
  Authors
Giepmans BN.
  Title
Gap junctions and connexin-interacting proteins.
  Journal
Cardiovasc Res 62:233-45 (2004)
DOI:10.1016/j.cardiores.2003.12.009
Reference
PMID:15955302
  Authors
Laird DW.
  Title
Connexin phosphorylation as a regulatory event linked to gap junction internalization and degradation.
  Journal
Biochim Biophys Acta 1711:172-82 (2005)
DOI:10.1016/j.bbamem.2004.09.009
Reference
PMID:15033579
  Authors
Peracchia C.
  Title
Chemical gating of gap junction channels; roles of calcium, pH and calmodulin.
  Journal
Biochim Biophys Acta 1662:61-80 (2004)
DOI:10.1016/j.bbamem.2003.10.020
Reference
PMID:15033578
  Authors
Bukauskas FF, Verselis VK.
  Title
Gap junction channel gating.
  Journal
Biochim Biophys Acta 1662:42-60 (2004)
DOI:10.1016/j.bbamem.2004.01.008
Related
pathway
hsa04010  MAPK signaling pathway
hsa04020  Calcium signaling pathway
hsa04060  Cytokine-cytokine receptor interaction
hsa04070  Phosphatidylinositol signaling system
hsa04080  Neuroactive ligand-receptor interaction
KO pathway
ko04540   

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