KEGG   PATHWAY: fpg04270
Entry
fpg04270                    Pathway                                
Name
Vascular smooth muscle contraction - Falco peregrinus (peregrine falcon)
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
fpg04270  Vascular smooth muscle contraction
fpg04270

Other DBs
GO: 0014829
Organism
Falco peregrinus (peregrine falcon) [GN:fpg]
Gene
101923570  ADRA1A; adrenoceptor alpha 1A [KO:K04135]
101920857  ADRA1B; adrenoceptor alpha 1B [KO:K04136]
101912258  ADRA1D; adrenoceptor alpha 1D [KO:K04137]
101920124  AGT; angiotensinogen [KO:K09821]
101914397  AGTR1; angiotensin II receptor type 1 [KO:K04166]
101921903  EDN1; endothelin 1 [KO:K16366]
101920416  EDN2; endothelin-2 [KO:K16367]
101918418  EDNRA; endothelin receptor type A [KO:K04197]
101911252  vasotocin-neurophysin VT [KO:K05242]
101921811  AVPR1A; arginine vasopressin receptor 1A [KO:K04226]
101920095  AVPR1B; arginine vasopressin receptor 1B [KO:K04227]
101912464  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101923890  GNA11; G protein subunit alpha 11 [KO:K04635]
101916058  basic phospholipase A2 Cdr-13-like [KO:K01047] [EC:3.1.1.4]
101923379  phospholipase A2, membrane associated-like [KO:K01047] [EC:3.1.1.4]
101924753  PLA2G10; phospholipase A2 group X [KO:K01047] [EC:3.1.1.4]
101912549  PLA2G1B; phospholipase A2 group IB [KO:K01047] [EC:3.1.1.4]
101923873  PLA2G12B; phospholipase A2 group XIIB [KO:K01047] [EC:3.1.1.4]
101917413  PLA2G12A; phospholipase A2 group XIIA [KO:K01047] [EC:3.1.1.4]
101923767  group 10 secretory phospholipase A2-like [KO:K01047] [EC:3.1.1.4]
101922121  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
101920043  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
101918580  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
101915779  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
101925028  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
101924845  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
101925011  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
101922643  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
101918608  PLA2G6; phospholipase A2 group VI [KO:K16343] [EC:3.1.1.4]
101915596  KCNMA1; potassium calcium-activated channel subfamily M alpha 1 [KO:K04936]
106112245  KCNU1; potassium calcium-activated channel subfamily U member 1 [KO:K05274]
101915137  KCNMB1; potassium calcium-activated channel subfamily M regulatory beta subunit 1 [KO:K04937]
101910854  KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938]
101916694  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
101912795  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
101922071  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
101914764  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
101923747  calmodulin, striated muscle [KO:K02183]
101916818  CALM2; calmodulin 2 [KO:K02183]
101919099  CALM1; calmodulin 1 [KO:K02183]
101912097  CALML4; calmodulin like 4 [KO:K02183]
101910574  myosin light chain kinase, smooth muscle-like [KO:K00907] [EC:2.7.11.18]
101922032  MYLK2; myosin light chain kinase 2 [KO:K00907] [EC:2.7.11.18]
101922066  myosin light chain kinase 3-like [KO:K00907] [EC:2.7.11.18]
101922502  MYLK; myosin light chain kinase [KO:K00907] [EC:2.7.11.18]
101917440  MYLK3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
101911603  myosin regulatory light polypeptide 9 [KO:K12755]
101915683  MYH10; myosin heavy chain 10 [KO:K10352]
101916325  MYH9; myosin heavy chain 9 [KO:K10352]
101924468  MYH11; myosin heavy chain 11 [KO:K10352]
101916711  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
101922366  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
101912415  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
101916606  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
101920370  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101911646  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101914699  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
101912011  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
101910888  CACNG7; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101920231  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
101917755  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
101912293  PRKCH; protein kinase C eta [KO:K18051] [EC:2.7.11.13]
101923479  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
101919653  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
101911761  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
101924998  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101924296  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101914611  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101915381  CALD1; caldesmon 1 [KO:K12327]
101915277  ACTA2; actin, alpha 2, smooth muscle, aorta [KO:K12313]
101922067  ACTG2; actin, gamma 2, smooth muscle, enteric [KO:K12315]
101924787  PPP1CC; protein phosphatase 1 catalytic subunit gamma [KO:K06269] [EC:3.1.3.16]
101913968  PPP1CA; protein phosphatase 1 catalytic subunit alpha [KO:K06269] [EC:3.1.3.16]
101916649  PPP1CB; protein phosphatase 1 catalytic subunit beta [KO:K06269] [EC:3.1.3.16]
101914871  PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270]
101915795  PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
101917262  GNA12; G protein subunit alpha 12 [KO:K04346]
101922831  GNA13; G protein subunit alpha 13 [KO:K04639]
101920266  ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532]
101920114  ARHGEF11; Rho guanine nucleotide exchange factor 11 [KO:K12331]
101911200  RHOA; ras homolog family member A [KO:K04513]
101913286  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
101916990  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
101924881  ADORA2A; adenosine A2a receptor [KO:K04266]
101913216  ADORA2B; adenosine A2b receptor [KO:K04267]
101912741  CALCB; calcitonin related polypeptide beta [KO:K12332]
101924203  ADM; adrenomedullin [KO:K12333]
101914009  CALCRL; calcitonin receptor like receptor [KO:K04577]
101915404  RAMP2; receptor activity modifying protein 2 [KO:K08448]
101911976  receptor activity-modifying protein 3-like [KO:K08449]
101922321  GNAS; GNAS complex locus [KO:K04632]
101914769  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
101911647  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
101921567  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
101922323  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
101916278  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
101914615  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
101921528  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
101921768  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
101921803  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
101920851  NPPA; natriuretic peptide A [KO:K12334]
106112381  C-type natriuretic peptide-like [KO:K12336]
101916740  NPR2; natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
101920659  atrial natriuretic peptide receptor 2-like [KO:K12324] [EC:4.6.1.2]
101914750  PRKG1; protein kinase, cGMP-dependent, type I [KO:K07376] [EC:2.7.11.12]
101919522  MRVI1; murine retrovirus integration site 1 homolog [KO:K12337]
101922339  GUCY1A3; guanylate cyclase 1 soluble subunit alpha [KO:K12318] [EC:4.6.1.2]
101914436  GUCY1A2; guanylate cyclase 1 soluble subunit alpha 2 [KO:K12318] [EC:4.6.1.2]
101920979  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:4.6.1.2]
101915374  GUCY1B3; guanylate cyclase 1 soluble subunit beta [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
fpg00590  Arachidonic acid metabolism
fpg04020  Calcium signaling pathway
KO pathway
ko04270   
LinkDB

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