KEGG   PATHWAY: amj04270
Entry
amj04270                    Pathway                                
Name
Vascular smooth muscle contraction - Alligator mississippiensis (American alligator)
Description
The vascular smooth muscle cell (VSMC) is a highly specialized cell whose principal function is contraction. On contraction, VSMCs shorten, thereby decreasing the diameter of a blood vessel to regulate the blood flow and pressure.
The principal mechanisms that regulate the contractile state of VSMCs are changes in cytosolic Ca2+ concentration ([Ca2+]c). In response to vasoconstrictor stimuli, Ca2+ is mobilized from intracellular stores and/or the extracellular space to increase [Ca2+]c in VSMCs. The increase in [Ca2+]c, in turn, activates the Ca2+-CaM-MLCK pathway and stimulates MLC20 phosphorylation, leading to myosin-actin interactions and, hence, the development of contractile force. The sensitivity of contractile myofilaments or MLC20 phosphorylation to Ca2+ can be secondarily modulated by other signaling pathways. During receptor stimulation, the contractile force is greatly enhanced by the inhibition of myosin phosphatase. Rho/Rho kinase, PKC, and arachidonic acid have been proposed to play a pivotal role in this enhancement.
The signaling events that mediate relaxation include the removal of a contractile agonist (passive relaxation) and activation of cyclic nucleotide-dependent signaling pathways in the continued presence of a contractile agonist (active relaxation). Active relaxation occurs through the inhibition of both Ca2+ mobilization and myofilament Ca2+ sensitivity in VSMCs.
Class
Organismal Systems; Circulatory system
Pathway map
amj04270  Vascular smooth muscle contraction
amj04270

Other DBs
GO: 0014829
Organism
Alligator mississippiensis (American alligator) [GN:amj]
Gene
102557676  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
102563347  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
102570643  AGT; angiotensinogen [KO:K09821]
102569750  AGTR1; angiotensin II receptor type 1 [KO:K04166]
102571363  EDN1; endothelin 1 [KO:K16366]
102570898  EDN2; endothelin 2 [KO:K16367]
102560952  EDN3; endothelin 3 [KO:K05227]
102558473  EDNRA; endothelin receptor type A [KO:K04197]
102569046  AVP; vasotocin-neurophysin VT [KO:K05242]
102559961  AVPR1A; arginine vasopressin receptor 1A [KO:K04226]
102568245  AVPR1B; arginine vasopressin receptor 1B [KO:K04227]
102565550  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102565314  GNA11; G protein subunit alpha 11 [KO:K04635]
102577237  PLA2G12B; phospholipase A2 group XIIB [KO:K01047] [EC:3.1.1.4]
102563866  PLA2G10; phospholipase A2 group X [KO:K01047] [EC:3.1.1.4]
102561536  phospholipase A2, minor isoenzyme [KO:K01047] [EC:3.1.1.4]
102570192  PLA2G1B; phospholipase A2 group IB [KO:K01047] [EC:3.1.1.4]
102572657  PLA2G3; phospholipase A2 group III [KO:K01047] [EC:3.1.1.4]
102571295  phospholipase A2 homolog otoconin-22 [KO:K01047] [EC:3.1.1.4]
102567413  PLA2G2D; uncharacterized LOC102567413 [KO:K01047] [EC:3.1.1.4]
102567178  acidic phospholipase A2 PLA-1-like [KO:K01047] [EC:3.1.1.4]
102576954  group 10 secretory phospholipase A2-like [KO:K01047] [EC:3.1.1.4]
102572276  PLA2G12A; phospholipase A2 group XIIA [KO:K01047] [EC:3.1.1.4]
102571708  cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102572619  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102571930  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
102571167  cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
106736657  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
102572385  cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102573324  PLA2G4F; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
102568256  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
102572848  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102573092  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
102568705  PLA2G4F.1; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102570036  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
102564564  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
106736888  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
102564541  KCNU1; potassium calcium-activated channel subfamily U member 1 [KO:K05274]
102573672  KCNMB1; potassium calcium-activated channel subfamily M regulatory beta subunit 1 [KO:K04937]
102572400  KCNMB2; potassium calcium-activated channel subfamily M regulatory beta subunit 2 [KO:K04938]
102567213  KCNMB4; potassium calcium-activated channel subfamily M regulatory beta subunit 4 [KO:K04941]
102575519  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
102576817  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102563169  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102563699  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102574007  CALM1; calmodulin 1 [KO:K02183]
102573656  CALM2; calmodulin 2 [KO:K02183]
102558596  CALM3; calmodulin [KO:K02183]
102558691  calmodulin-alpha [KO:K02183]
102561470  CALML6; calmodulin like 6 [KO:K02183]
102577125  CALML4; calmodulin like 4 [KO:K02183]
102557905  myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
102561520  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
102568638  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
102574082  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
102575999  MYL6; myosin light polypeptide 6 [KO:K12751]
102576229  MYL6B; myosin light chain 6B [KO:K12751]
102575766  MYL9; myosin light chain 9 [KO:K12755]
102559664  MYH10; myosin heavy chain 10 [KO:K10352]
102560042  MYH9; myosin heavy chain 9 [KO:K10352]
102574262  MYH11; myosin heavy chain 11 [KO:K10352]
102574445  myosin-10 [KO:K10352]
102576994  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102572359  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102566880  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102560430  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102561752  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102570264  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102567087  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102572836  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102572486  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102574559  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102571623  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
102576791  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
102565039  PRKCH; protein kinase C eta [KO:K18051] [EC:2.7.11.13]
106737047  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
106737102  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102576986  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102563228  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
106736997  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106737342  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102561718  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109282845  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
102568148  CALD1; caldesmon 1 [KO:K12327]
102577392  ACTA2; actin, alpha 2, smooth muscle, aorta [KO:K12313]
102574175  ACTG2; actin, gamma 2, smooth muscle, enteric [KO:K12315]
102564933  PPP1R14A; protein phosphatase 1 regulatory inhibitor subunit 14A [KO:K12328]
102560817  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
102564750  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
102565419  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
102562278  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
102561475  PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
102559388  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
102559993  GNA12; G protein subunit alpha 12 [KO:K04346]
102568562  GNA13; G protein subunit alpha 13 [KO:K04639]
102569441  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
106737254  ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330]
102571684  rho guanine nucleotide exchange factor 11 [KO:K12331]
102560127  transforming protein RhoA-like [KO:K04513]
102563558  RHOA; ras homolog family member A [KO:K04513]
102558298  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
102572451  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
102571514  ADORA2A; adenosine A2a receptor [KO:K04266]
106739353  adenosine receptor A1-like [KO:K04266]
102565084  ADORA2B; adenosine A2b receptor [KO:K04267]
102558362  PTGIR; prostaglandin I2 (prostacyclin) receptor (IP) [KO:K04263]
102564694  CALCB; calcitonin related polypeptide beta [KO:K12332]
102561213  ADM; adrenomedullin [KO:K12333]
106737861  ADM [KO:K12333]
109284541  ADM2; adrenomedullin 2 [KO:K25343]
102572298  CALCRL; calcitonin receptor like receptor [KO:K04577]
106737204  RAMP1; receptor activity modifying protein 1 [KO:K08447]
102566244  RAMP2; receptor activity modifying protein 2 [KO:K08448]
102564815  RAMP3; receptor activity modifying protein 3 [KO:K08449]
102563836  GNAS; GNAS complex locus [KO:K04632]
102573818  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102562034  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102566746  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102558956  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102562224  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102573402  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102566330  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102562540  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102574362  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102572143  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
106737076  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102572997  NPPB; natriuretic peptides A [KO:K12334]
102576972  natriuretic peptides A-like [KO:K12334]
106736703  NPR1; natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
102572314  atrial natriuretic peptide receptor 1 [KO:K12324] [EC:4.6.1.2]
102573015  PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
102570186  MRVI1; murine retrovirus integration site 1 homolog [KO:K12337]
106737232  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
102569074  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
102565558  GUCY1B3; guanylate cyclase 1 soluble subunit beta [KO:K12319] [EC:4.6.1.2]
106737496  guanylate cyclase soluble subunit beta-2 [KO:K12319] [EC:4.6.1.2]
102561438  guanylate cyclase soluble subunit beta-2 [KO:K12319] [EC:4.6.1.2]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00212  Adenosine
C00219  Arachidonate
C00238  Potassium cation
C00533  Nitric oxide
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00942  3',5'-Cyclic GMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01312  Prostaglandin I2
C14748  20-HETE
C14768  5,6-EET
C14769  8,9-EET
C14770  11,12-EET
C14771  14,15-EET
Reference
PMID:17458653
  Authors
Akata T
  Title
Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in vascular smooth muscle cells.
  Journal
J Anesth 21:232-42 (2007)
DOI:10.1007/s00540-006-0488-4
Reference
PMID:12689814
  Authors
Ogut O, Brozovich FV
  Title
Regulation of force in vascular smooth muscle.
  Journal
J Mol Cell Cardiol 35:347-55 (2003)
DOI:10.1016/S0022-2828(03)00045-2
Reference
PMID:16339747
  Authors
Hilgers RH, Webb RC
  Title
Molecular aspects of arterial smooth muscle contraction: focus on Rho.
  Journal
Exp Biol Med (Maywood) 230:829-35 (2005)
DOI:10.1177/153537020523001107
Reference
PMID:12693609
  Authors
Schlossmann J, Feil R, Hofmann F
  Title
Signaling through NO and cGMP-dependent protein kinases.
  Journal
Ann Med 35:21-7 (2003)
DOI:10.1080/07853890310004093
Reference
PMID:16870827
  Authors
Mehta PK, Griendling KK
  Title
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.
  Journal
Am J Physiol Cell Physiol 292:C82-97 (2007)
DOI:10.1152/ajpcell.00287.2006
Reference
PMID:19120701
  Authors
Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG
  Title
Smooth muscle signalling pathways in health and disease.
  Journal
J Cell Mol Med 12:2165-80 (2008)
DOI:10.1111/j.1582-4934.2008.00552.x
Reference
PMID:11165670
  Authors
Fukata Y, Amano M, Kaibuchi K
  Title
Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.
  Journal
Trends Pharmacol Sci 22:32-9 (2001)
DOI:10.1016/S0165-6147(00)01596-0
Reference
PMID:17158339
  Authors
Dimopoulos GJ, Semba S, Kitazawa K, Eto M, Kitazawa T
  Title
Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle.
  Journal
Circ Res 100:121-9 (2007)
DOI:10.1161/01.RES.0000253902.90489.df
Reference
PMID:17200683
  Authors
Hynynen MM, Khalil RA
  Title
The vascular endothelin system in hypertension--recent patents and discoveries.
  Journal
Recent Pat Cardiovasc Drug Discov 1:95-108 (2006)
DOI:10.2174/157489006775244263
Reference
PMID:15269340
  Authors
Brain SD, Grant AD
  Title
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
  Journal
Physiol Rev 84:903-34 (2004)
DOI:10.1152/physrev.00037.2003
Reference
PMID:11773611
  Authors
Roman RJ
  Title
P-450 metabolites of arachidonic acid in the control of cardiovascular function.
  Journal
Physiol Rev 82:131-85 (2002)
DOI:10.1152/physrev.00021.2001
Reference
PMID:18040024
  Authors
Surks HK
  Title
cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms.
  Journal
Circ Res 101:1078-80 (2007)
DOI:10.1161/CIRCRESAHA.107.165779
Reference
PMID:15026027
  Authors
Vanhoutte PM
  Title
Endothelium-dependent hyperpolarizations: the history.
  Journal
Pharmacol Res 49:503-8 (2004)
DOI:10.1016/j.phrs.2003.11.015
Reference
PMID:10221985
  Authors
Davis MJ, Hill MA
  Title
Signaling mechanisms underlying the vascular myogenic response.
  Journal
Physiol Rev 79:387-423 (1999)
DOI:10.1152/physrev.1999.79.2.387
Reference
PMID:11679404
  Authors
Fleming I.
  Title
Cytochrome p450 and vascular homeostasis.
  Journal
Circ Res 89:753-62 (2001)
DOI:10.1161/hh2101.099268
Reference
PMID:10911373
  Authors
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP
  Title
Molecular mechanism of cGMP-mediated smooth muscle relaxation.
  Journal
J Cell Physiol 184:409-20 (2000)
DOI:10.1002/1097-4652(200009)184:3<409::AID-JCP16>3.0.CO;2-K
Reference
PMID:18552454
  Authors
Ko EA, Han J, Jung ID, Park WS
  Title
Physiological roles of K+ channels in vascular smooth muscle cells.
  Journal
J Smooth Muscle Res 44:65-81 (2008)
DOI:10.1540/jsmr.44.65
Reference
PMID:18703404
  Authors
Woodard GE, Rosado JA
  Title
Natriuretic peptides in vascular physiology and pathology.
  Journal
Int Rev Cell Mol Biol 268:59-93 (2008)
DOI:10.1016/S1937-6448(08)00803-4
Reference
PMID:11709400
  Authors
Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG
  Title
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide.
  Journal
Am J Physiol Heart Circ Physiol 281:H2337-65 (2001)
DOI:10.1152/ajpheart.2001.281.6.H2337
Reference
PMID:15725705
  Authors
Hirano K, Hirano M, Kanaide H
  Title
Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular smooth muscle.
  Journal
J Smooth Muscle Res 40:219-36 (2004)
DOI:10.1540/jsmr.40.219
Reference
PMID:9458738
  Authors
Freeman EJ, Ruehr ML, Dorman RV
  Title
ANG II-induced translocation of cytosolic PLA2 to the nucleus in vascular smooth muscle cells.
  Journal
Am J Physiol 274:C282-8 (1998)
DOI:10.1152/ajpcell.1998.274.1.C282
Reference
PMID:12060106
  Authors
Murphy TV, Spurrell BE, Hill MA
  Title
Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine phosphorylation pathways.
  Journal
Clin Exp Pharmacol Physiol 29:612-9 (2002)
DOI:10.1046/j.1440-1681.2002.03698.x
Related
pathway
amj00590  Arachidonic acid metabolism
amj04020  Calcium signaling pathway
KO pathway
ko04270   
LinkDB

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