KEGG   PATHWAY: aml04270
Entry
aml04270                    Pathway                                
Name
Vascular smooth muscle contraction - Ailuropoda melanoleuca (giant panda)
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
aml04270  Vascular smooth muscle contraction
aml04270

Other DBs
GO: 0014829
Organism
Ailuropoda melanoleuca (giant panda) [GN:aml]
Gene
100463545  [KO:K01047] [EC:3.1.1.4]
100463582  KCNMB1; calcium-activated potassium channel subunit beta-1 isoform X1 [KO:K04937]
100463798  PLA2G2F; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100463833  KCNMB4; calcium-activated potassium channel subunit beta-4 isoform X2 [KO:K04941]
100464051  PLA2G2C; putative inactive group IIC secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
100464166  ADORA2B; adenosine receptor A2b [KO:K04267]
100464499  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100464853  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100465232  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100465369  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
100465571  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100466003  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
100466213  [KO:K12332]
100466272  RAMP1; receptor activity-modifying protein 1 isoform X1 [KO:K08447]
100466547  MYH9; myosin-9 [KO:K10352]
100466578  [KO:K12332]
100466702  IRAG1; protein MRVI1 isoform X1 [KO:K12337]
100466965  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100467118  CALCRL; calcitonin gene-related peptide type 1 receptor [KO:K04577]
100467161  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X8 [KO:K04958]
100467700  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100468070  [KO:K12319] [EC:4.6.1.2]
100468242  MYH14; myosin-14 [KO:K10352]
100468252  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X2 [KO:K04345] [EC:2.7.11.11]
100468661  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
100468967  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
100469231  [KO:K04632]
100469244  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
100469346  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100469587  [KO:K05242]
100469628  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100469689  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
100469861  NPPA; natriuretic peptides A [KO:K12334]
100469987  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
100469999  MYL6B; myosin light chain 6B [KO:K12751]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100470061  [KO:K07425] [EC:1.14.14.80]
100470069  PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X8 [KO:K12329]
100470116  NPPB; natriuretic peptides B [KO:K12335]
100470137  AGT; angiotensinogen [KO:K09821]
100470240  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
100470421  MYL6; myosin light polypeptide 6 isoform X2 [KO:K12751]
100470490  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
100470496  ACTA2; actin, aortic smooth muscle [KO:K12313]
100470909  CALM2; calmodulin-2 [KO:K02183]
100470926  EDN1; endothelin-1 [KO:K16366]
100470998  [KO:K16342] [EC:3.1.1.4]
100471078  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
100471164  ADCY3; adenylate cyclase type 3 isoform X2 [KO:K08043] [EC:4.6.1.1]
100471220  AGTR1; type-1 angiotensin II receptor [KO:K04166]
100471349  PLA2G10; group 10 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100471456  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100471509  KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274]
100471747  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100471873  PTGIR; prostacyclin receptor [KO:K04263]
100471940  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
100472122  CALM3; calmodulin-3 [KO:K02183]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100472577  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X4 [KO:K16343] [EC:3.1.1.4]
100472601  NPR2; atrial natriuretic peptide receptor 2 isoform X6 [KO:K12324] [EC:4.6.1.2]
100472771  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
100472777  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100472835  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
100472876  RAMP2; LOW QUALITY PROTEIN: receptor activity-modifying protein 2 [KO:K08448]
100472913  EDN3; endothelin-3 isoform X1 [KO:K05227]
100473050  PPP1R14A; protein phosphatase 1 regulatory subunit 14A isoform X1 [KO:K12328]
100473195  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100473263  KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X23 [KO:K04936]
100473449  MYH10; myosin-10 isoform X2 [KO:K10352]
100473453  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
100473488  PLA2G1B; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100473680  [KO:K04632]
100473684  ADM; ADM isoform X1 [KO:K12333]
100473819  EDN2; endothelin-2 isoform X1 [KO:K16367]
100474121  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100474254  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
100474277  EDNRA; endothelin-1 receptor [KO:K04197]
100474469  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
100474482  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
100474521  PRKCH; protein kinase C eta type isoform X2 [KO:K18051] [EC:2.7.11.13]
100474572  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
100474673  ARHGEF11; LOW QUALITY PROTEIN: rho guanine nucleotide exchange factor 11 [KO:K12331]
100474779  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100475213  ADM2; protein ADM2 [KO:K25343]
100475358  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100475955  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
100476029  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100476427  AVPR1B; vasopressin V1b receptor [KO:K04227]
100476495  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100476723  RHOA; transforming protein RhoA [KO:K04513]
100476728  ACTG2; actin, gamma-enteric smooth muscle [KO:K12315]
100476917  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
100476922  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
100477081  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100477888  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100478212  PLA2G2E; group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100478431  ADORA2A; adenosine receptor A2a [KO:K04266]
100478600  CALML6; calmodulin-like protein 6 [KO:K02183]
100478732  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100479059  PLA2G3; group 3 secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
100479715  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X3 [KO:K04850]
100479868  CALD1; caldesmon isoform X4 [KO:K12327]
100479899  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
100480509  RAMP3; receptor activity-modifying protein 3 [KO:K08449]
100480603  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
100480927  PLA2G12B; group XIIB secretory phospholipase A2-like protein isoform X1 [KO:K01047] [EC:3.1.1.4]
100481177  CALM1; calmodulin-1 [KO:K02183]
100481263  MYLK; myosin light chain kinase, smooth muscle isoform X5 [KO:K00907] [EC:2.7.11.18]
100481364  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X2 [KO:K12319] [EC:4.6.1.2]
100481505  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
100481755  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100481918  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100482519  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100482619  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
100482658  [KO:K04136]
100483617  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
100483809  KCNMB2; calcium-activated potassium channel subunit beta-2 isoform X2 [KO:K04938]
100483836  NPPC; C-type natriuretic peptide [KO:K12336]
100483995  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
100484063  KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X1 [KO:K04939]
100484519  [KO:K02183]
100484647  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100484745  PLA2G5; calcium-dependent phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100484770  [KO:K02183]
100484803  MYH11; myosin-11 isoform X1 [KO:K10352]
100484939  AVPR1A; vasopressin V1a receptor [KO:K04226]
105234638  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
117796269  PLA2G2D; group IID secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
117798907  [KO:K12751]
117799706  [KO:K02183]
117801375  [KO:K04136]
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
aml00590  Arachidonic acid metabolism
aml04020  Calcium signaling pathway
KO pathway
ko04270   

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