KEGG   PATHWAY: mna04270
mna04270                    Pathway                                

Vascular smooth muscle contraction - Miniopterus natalensis
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.
Organismal Systems; Circulatory system
Pathway map
mna04270  Vascular smooth muscle contraction

Other DBs
GO: 0014829
Miniopterus natalensis [GN:mna]
107529888  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
107537855  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
107536281  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
107524243  AGT; angiotensinogen [KO:K09821]
107544042  AGTR1; type-1 angiotensin II receptor [KO:K04166]
107530403  EDN1; endothelin-1 [KO:K16366]
107531168  EDN2; endothelin-2 isoform X1 [KO:K16367]
107529292  EDN3; endothelin-3 isoform X1 [KO:K05227]
107532511  EDNRA; endothelin-1 receptor [KO:K04197]
107536288  AVP; vasopressin-neurophysin 2-copeptin [KO:K05242]
107527253  AVPR1A; vasopressin V1a receptor [KO:K04226]
107539423  AVPR1B; vasopressin V1b receptor [KO:K04227]
107544926  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107544328  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
107526176  PLA2G3; LOW QUALITY PROTEIN: group 3 secretory phospholipase A2 [KO:K01047] [EC:]
107534370  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:]
107538317  PLA2G2A; phospholipase A2, membrane associated [KO:K01047] [EC:]
107545802  PLA2G12B; group XIIB secretory phospholipase A2-like protein [KO:K01047] [EC:]
107538382  PLA2G2E; group IIE secretory phospholipase A2 [KO:K01047] [EC:]
107538385  PLA2G2C; putative inactive group IIC secretory phospholipase A2 [KO:K01047] [EC:]
107528479  PLA2G1B; phospholipase A2 [KO:K01047] [EC:]
107524380  group 10 secretory phospholipase A2-like [KO:K01047] [EC:]
107538464  PLA2G2F; group IIF secretory phospholipase A2 [KO:K01047] [EC:]
107538466  PLA2G5; calcium-dependent phospholipase A2 [KO:K01047] [EC:]
107538467  PLA2G2D; group IID secretory phospholipase A2 [KO:K01047] [EC:]
107546298  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:]
107536544  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:]
107536549  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:]
107536550  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:]
107536561  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:]
107544563  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 [KO:K16343] [EC:]
107545799  KCNMA1; calcium-activated potassium channel subunit alpha-1 [KO:K04936]
107540345  KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
107541098  KCNMB2; calcium-activated potassium channel subunit beta-2 isoform X1 [KO:K04938]
107541085  KCNMB3; calcium-activated potassium channel subunit beta-3 [KO:K04939]
107526648  KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941]
107546425  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
107534931  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
107541372  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
107536018  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
107542429  CALML3; calmodulin-like protein 3 [KO:K02183]
107542435  CALML5; calmodulin-like protein 5 [KO:K02183]
107536794  CALM3; calmodulin [KO:K02183]
107540147  CALML6; calmodulin-like protein 6 [KO:K02183]
107544318  CALM2; calmodulin isoform X1 [KO:K02183]
107531584  CALM1; calmodulin [KO:K02183]
107525969  CALML4; calmodulin-like protein 4 [KO:K02183]
107542256  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:]
107527759  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:]
107533389  myosin light polypeptide 6-like [KO:K12751]
107546178  MYL6B; myosin light chain 6B isoform X1 [KO:K12751]
107546180  MYL6; myosin light polypeptide 6 isoform X1 [KO:K12751]
107544330  myosin regulatory light polypeptide 9 [KO:K12755]
107542167  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
107524357  MYH11; myosin-11 [KO:K10352]
107531785  MYH14; myosin-14 [KO:K10352]
107544543  MYH10; myosin-10 [KO:K10352]
107544784  MYH9; myosin-9 [KO:K10352]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
107529142  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
107525255  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
107541588  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107538300  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
107544745  PRKCB; protein kinase C beta type [KO:K19662] [EC:]
107540426  PRKCG; protein kinase C gamma type [KO:K19663] [EC:]
107534935  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:]
107530341  protein kinase C epsilon type isoform X1 [KO:K18050] [EC:]
107525926  PRKCH; protein kinase C eta type [KO:K18051] [EC:]
107542460  PRKCQ; protein kinase C theta type [KO:K18052] [EC:]
107541381  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:]
107531103  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:]
107534729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
107533801  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
107525695  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
107544308  CALD1; caldesmon isoform X1 [KO:K12327]
107543359  ACTA2; actin, aortic smooth muscle [KO:K12313]
107529268  ACTG2; actin, gamma-enteric smooth muscle [KO:K12315]
107532213  PPP1R14A; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 14A [KO:K12328]
107534692  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:]
107533957  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:]
107529564  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:]
107526828  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
107536013  PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329]
107541310  PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457]
107541162  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
107538305  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
107533084  ARHGEF12; rho guanine nucleotide exchange factor 12 [KO:K07532]
107534237  ARHGEF1; rho guanine nucleotide exchange factor 1 [KO:K12330]
107543803  ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331]
107529450  RHOA; transforming protein RhoA [KO:K04513]
107535907  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:]
107542396  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:]
107530474  ADORA2A; adenosine receptor A2a [KO:K04266]
107524507  ADORA2B; adenosine receptor A2b [KO:K04267]
107536793  PTGIR; prostacyclin receptor [KO:K04263]
107546732  calcitonin gene-related peptide 2-like [KO:K12332]
107546743  calcitonin gene-related peptide 1-like [KO:K12332]
107546742  calcitonin gene-related peptide 2-like [KO:K12332]
107537041  CALCRL; calcitonin gene-related peptide type 1 receptor isoform X1 [KO:K04577]
107529999  RAMP1; receptor activity-modifying protein 1 [KO:K08447]
107528842  RAMP2; receptor activity-modifying protein 2 [KO:K08448]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:]
107531532  NPPA; natriuretic peptides A [KO:K12334]
107543755  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:]
107530741  NPPC; C-type natriuretic peptide [KO:K12336]
107530742  C-type natriuretic peptide-like [KO:K12336]
107544941  NPR2; atrial natriuretic peptide receptor 2 isoform X1 [KO:K12324] [EC:]
107543282  PRKG1; cGMP-dependent protein kinase 1 [KO:K07376] [EC:]
107532275  MRVI1; protein MRVI1 isoform X1 [KO:K12337]
107527534  GUCY1A3; guanylate cyclase soluble subunit alpha-3 [KO:K12318] [EC:]
107532921  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:]
107527535  GUCY1B3; guanylate cyclase soluble subunit beta-1 [KO:K12319] [EC:]
107537733  guanylate cyclase soluble subunit beta-2-like [KO:K12319] [EC:]
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
Akata T
Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in vascular smooth muscle cells.
J Anesth 21:232-42 (2007)
Ogut O, Brozovich FV
Regulation of force in vascular smooth muscle.
J Mol Cell Cardiol 35:347-55 (2003)
Hilgers RH, Webb RC
Molecular aspects of arterial smooth muscle contraction: focus on Rho.
Exp Biol Med (Maywood) 230:829-35 (2005)
Schlossmann J, Feil R, Hofmann F
Signaling through NO and cGMP-dependent protein kinases.
Ann Med 35:21-7 (2003)
Mehta PK, Griendling KK
Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.
Am J Physiol Cell Physiol 292:C82-97 (2007)
Kim HR, Appel S, Vetterkind S, Gangopadhyay SS, Morgan KG
Smooth muscle signalling pathways in health and disease.
J Cell Mol Med 12:2165-80 (2008)
Fukata Y, Amano M, Kaibuchi K
Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells.
Trends Pharmacol Sci 22:32-9 (2001)
Dimopoulos GJ, Semba S, Kitazawa K, Eto M, Kitazawa T
Ca2+-dependent rapid Ca2+ sensitization of contraction in arterial smooth muscle.
Circ Res 100:121-9 (2007)
Hynynen MM, Khalil RA
The vascular endothelin system in hypertension--recent patents and discoveries.
Recent Pat Cardiovasc Drug Discov 1:95-108 (2006)
Brain SD, Grant AD
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
Physiol Rev 84:903-34 (2004)
Roman RJ
P-450 metabolites of arachidonic acid in the control of cardiovascular function.
Physiol Rev 82:131-85 (2002)
Surks HK
cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms.
Circ Res 101:1078-80 (2007)
Vanhoutte PM
Endothelium-dependent hyperpolarizations: the history.
Pharmacol Res 49:503-8 (2004)
Davis MJ, Hill MA
Signaling mechanisms underlying the vascular myogenic response.
Physiol Rev 79:387-423 (1999)
Fleming I.
Cytochrome p450 and vascular homeostasis.
Circ Res 89:753-62 (2001)
Carvajal JA, Germain AM, Huidobro-Toro JP, Weiner CP
Molecular mechanism of cGMP-mediated smooth muscle relaxation.
Ko EA, Han J, Jung ID, Park WS
Physiological roles of K+ channels in vascular smooth muscle cells.
J Smooth Muscle Res 44:65-81 (2008)
Woodard GE, Rosado JA
Natriuretic peptides in vascular physiology and pathology.
Int Rev Cell Mol Biol 268:59-93 (2008)
Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG
Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide.
Am J Physiol Heart Circ Physiol 281:H2337-65 (2001)
Hirano K, Hirano M, Kanaide H
Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular smooth muscle.
J Smooth Muscle Res 40:219-36 (2004)
Freeman EJ, Ruehr ML, Dorman RV
ANG II-induced translocation of cytosolic PLA2 to the nucleus in vascular smooth muscle cells.
Am J Physiol 274:C282-8 (1998)
Murphy TV, Spurrell BE, Hill MA
Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine phosphorylation pathways.
Clin Exp Pharmacol Physiol 29:612-9 (2002)
mna00590  Arachidonic acid metabolism
mna04020  Calcium signaling pathway
KO pathway

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