KEGG   PATHWAY: lav04270
Entry
lav04270                    Pathway                                
Name
Vascular smooth muscle contraction - Loxodonta africana (African savanna elephant)
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
lav04270  Vascular smooth muscle contraction
lav04270

Other DBs
GO: 0014829
Organism
Loxodonta africana (African savanna elephant) [GN:lav]
Gene
100653532  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
100653771  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
100653783  ADORA2A; adenosine receptor A2a [KO:K04266]
100654723  EDNRA; endothelin-1 receptor [KO:K04197]
100654995  ACTG2; actin, gamma-enteric smooth muscle [KO:K12315]
100655206  [KO:K04632]
100655239  ADM2; ADM2 [KO:K25343]
100655386  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
100655727  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100655811  MYH14; myosin-14 isoform X1 [KO:K10352]
100656201  KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X6 [KO:K04936]
100656346  EDN3; endothelin-3 [KO:K05227]
100656405  MYLK2; LOW QUALITY PROTEIN: myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
100656623  PLA2G3; group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100656672  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
100656966  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100657357  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
100657418  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
100657587  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100657612  [KO:K02183]
100657662  KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X3 [KO:K04939]
100657922  AVPR1B; vasopressin V1b receptor [KO:K04227]
100658208  [KO:K02183]
100658240  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100658490  PLA2G4A; cytosolic phospholipase A2 isoform X2 [KO:K16342] [EC:3.1.1.4]
100658510  KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938]
100658857  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
100658952  ACTA2; actin, aortic smooth muscle [KO:K12313]
100658962  CALML3; calmodulin-like protein 3 [KO:K02183]
100659079  AGTR1; type-1 angiotensin II receptor [KO:K04166]
100659245  PRKCD; protein kinase C delta type isoform X2 [KO:K06068] [EC:2.7.11.13]
100659328  PRKCH; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
100659377  PPP1R14A; protein phosphatase 1 regulatory subunit 14A [KO:K12328]
100659666  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
100659992  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100660199  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100660480  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100660583  NPPB; natriuretic peptides B [KO:K12335]
100660805  RAMP3; receptor activity-modifying protein 3 [KO:K08449]
100660875  NPPA; natriuretic peptides A [KO:K12334]
100661002  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
100661041  PTGIR; LOW QUALITY PROTEIN: prostacyclin receptor [KO:K04263]
100661616  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
100662471  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
100662745  PLA2G12B; group XIIB secretory phospholipase A2-like protein [KO:K01047] [EC:3.1.1.4]
100662779  GUCY1A2; guanylate cyclase soluble subunit alpha-2 [KO:K12318] [EC:4.6.1.2]
100663278  KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
100663448  ADCY9; LOW QUALITY PROTEIN: adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
100663507  CALM1; calmodulin-1 [KO:K02183]
100663829  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
100663946  GUCY1A1; guanylate cyclase soluble subunit alpha-3 isoform X1 [KO:K12318] [EC:4.6.1.2]
100664119  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
100664679  CALM2; calmodulin-2 [KO:K02183]
100664965  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
100665028  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100665157  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100665160  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 [KO:K16343] [EC:3.1.1.4]
100665374  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
100665477  AVPR1A; vasopressin V1a receptor [KO:K04226]
100665537  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100665634  MYLK4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
100665691  ADM; ADM isoform X2 [KO:K12333]
100667057  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100667623  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100667788  [KO:K05242]
100667845  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
100668259  ADRA1A; alpha-1A adrenergic receptor [KO:K04135]
100668402  MYH11; myosin-11 [KO:K10352]
100668504  KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941]
100668575  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
100668846  MYH10; myosin-10 [KO:K10352]
100669226  [KO:K04632]
100669550  PPP1R12C; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 12C [KO:K17457]
100669885  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
100670009  MYL6B; myosin light chain 6B [KO:K12751]
100670141  AGT; LOW QUALITY PROTEIN: angiotensinogen [KO:K09821]
100670244  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
100670299  MYL6; myosin light polypeptide 6 isoform X1 [KO:K12751]
100670617  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
100670906  PLA2G2C; putative inactive group IIC secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100670968  CALCRL; LOW QUALITY PROTEIN: calcitonin gene-related peptide type 1 receptor [KO:K04577]
100671072  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
100671190  PLA2G2F; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100671404  ARAF; serine/threonine-protein kinase A-Raf isoform X3 [KO:K08845] [EC:2.7.11.1]
100671475  PLA2G2D; group IID secretory phospholipase A2 isoform X1 [KO:K01047] [EC:3.1.1.4]
100671604  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100671733  PRKCG; LOW QUALITY PROTEIN: protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100671761  PLA2G5; calcium-dependent phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100671961  NPR1; atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
100671983  MYH9; LOW QUALITY PROTEIN: myosin-9 [KO:K10352]
100672052  [KO:K01047] [EC:3.1.1.4]
100672072  NPPC; C-type natriuretic peptide isoform X2 [KO:K12336]
100672078  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
100672344  [KO:K01047] [EC:3.1.1.4]
100672435  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
100672436  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
100672459  EDN1; endothelin-1 isoform X1 [KO:K16366]
100672909  [KO:K12332]
100672917  PLA2G2E; group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100673089  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
100673193  [KO:K12332]
100673301  ARHGEF11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331]
100673570  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
100673814  PPP1CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100673922  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X2 [KO:K06270]
100673973  RAMP2; receptor activity-modifying protein 2 [KO:K08448]
100673977  EDN2; endothelin-2 [KO:K16367]
100674245  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100674589  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X2 [KO:K12330]
100674649  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
100674724  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
100675131  PLA2G4D; LOW QUALITY PROTEIN: cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
100675139  ADORA2B; adenosine receptor A2b [KO:K04267]
100675231  PLA2G1B; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
100675383  KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274]
100675410  PLA2G4F; LOW QUALITY PROTEIN: cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
100675525  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
100675762  MRVI1; LOW QUALITY PROTEIN: protein MRVI1 [KO:K12337]
100675896  [KO:K04635]
100675940  PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X3 [KO:K12329]
100675999  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
100676051  [KO:K12319] [EC:4.6.1.2]
100676090  CALD1; caldesmon isoform X2 [KO:K12327]
100676444  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
100676492  NPR2; atrial natriuretic peptide receptor 2 [KO:K12324] [EC:4.6.1.2]
100677183  MYLK; myosin light chain kinase, smooth muscle isoform X2 [KO:K00907] [EC:2.7.11.18]
100677447  RHOA; transforming protein RhoA [KO:K04513]
104846176  [KO:K01047] [EC:3.1.1.4]
111752704  PLA2G10; group 10 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
111753010  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
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
lav00590  Arachidonic acid metabolism
lav04020  Calcium signaling pathway
KO pathway
ko04270   

DBGET integrated database retrieval system