KEGG   PATHWAY: dsp04270
Entry
dsp04270                    Pathway                                
Name
Vascular smooth muscle contraction - Dipodomys spectabilis (banner-tailed kangaroo rat)
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
dsp04270  Vascular smooth muscle contraction
dsp04270

Other DBs
GO: 0014829
Organism
Dipodomys spectabilis (banner-tailed kangaroo rat) [GN:dsp]
Gene
122095118  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
122095227  Agtr1; type-1 angiotensin II receptor [KO:K04166]
122095683  Rhoa; transforming protein RhoA [KO:K04513]
122095844  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122095888  Pla2g3; group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
122095929  Adora2a; adenosine receptor A2a [KO:K04266]
122096287  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122096833  Mylk; myosin light chain kinase, smooth muscle isoform X1 [KO:K00907] [EC:2.7.11.18]
122096857  Mylk3; myosin light chain kinase 3 [KO:K00907] [EC:2.7.11.18]
122097417  Arhgef1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
122097619  Ppp1r14a; protein phosphatase 1 regulatory subunit 14A [KO:K12328]
122097862  Gucy1b1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
122097873  Gucy1a1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
122097950  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
122098491  Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
122098764  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
122098776  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
122099052  Pla2g1b; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
122099331  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122099338  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
122099551  Cald1; caldesmon isoform X1 [KO:K12327]
122100399  Myh10; myosin-10 [KO:K10352]
122100994  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
122101010  Ramp2; receptor activity-modifying protein 2 [KO:K08448]
122101867  Kcnmb1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
122103331  Adora2b; adenosine receptor A2b [KO:K04267]
122103830  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
122104238  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
122104508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
122104536  Calm2; calmodulin-2 [KO:K02183]
122104544  Prkce; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
122104673  Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
122104709  [KO:K07425] [EC:1.14.14.80]
122104733  [KO:K07425] [EC:1.14.14.80]
122104750  [KO:K07425] [EC:1.14.14.80]
122105124  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
122105936  Braf; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
122106258  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
122106993  Edn1; endothelin-1 [KO:K16366]
122107276  Kcnmb3; calcium-activated potassium channel subunit beta-3 [KO:K04939]
122107285  Kcnmb2; calcium-activated potassium channel subunit beta-2 [KO:K04938]
122107574  Nppc; C-type natriuretic peptide [KO:K12336]
122107826  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122107987  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
122108123  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
122108136  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
122108406  [KO:K12751]
122108431  Mylk4; myosin light chain kinase family member 4 [KO:K00907] [EC:2.7.11.18]
122108760  Rock2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
122109161  Ppp1r12b; protein phosphatase 1 regulatory subunit 12B isoform X1 [KO:K12329]
122109366  Arhgef11; rho guanine nucleotide exchange factor 11 isoform X1 [KO:K12331]
122109556  Npr1; LOW QUALITY PROTEIN: atrial natriuretic peptide receptor 1 [KO:K12323] [EC:4.6.1.2]
122109721  Avpr1b; vasopressin V1b receptor [KO:K04227]
122110059  Prkch; protein kinase C eta type [KO:K18051] [EC:2.7.11.13]
122110410  Arhgef12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
122110671  Prkcg; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
122110725  Ppp1r12c; protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457]
122111510  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
122112253  Edn2; endothelin-2 isoform X1 [KO:K16367]
122112891  [KO:K12319] [EC:4.6.1.2]
122113156  Prkcq; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
122113235  Calml3; calmodulin-like protein 3 [KO:K02183]
122113280  Calml5; calmodulin-like protein 5 [KO:K02183]
122113292  Agt; angiotensinogen [KO:K09821]
122113375  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
122113573  Gna12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
122114391  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
122114401  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
122114427  Pla2g4e; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
122114429  Pla2g4f; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
122114610  [KO:K16342] [EC:3.1.1.4]
122114616  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
122115017  [KO:K04513]
122115018  Calcrl; calcitonin gene-related peptide type 1 receptor [KO:K04577]
122115232  Pla2g2d; group IID secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
122115288  Pla2g2a; phospholipase A2, membrane associated [KO:K01047] [EC:3.1.1.4]
122115300  Pla2g5; phospholipase A2 group V [KO:K01047] [EC:3.1.1.4]
122115334  Pla2g2c; putative inactive group IIC secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
122115335  Pla2g2f; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
122115336  Pla2g2e; group IIE secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
122115721  Prkg1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
122115806  Acta2; actin, aortic smooth muscle [KO:K12313]
122116145  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
122116532  Kcnma1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936]
122116562  Pla2g12b; group XIIB secretory phospholipase A2-like protein isoform X1 [KO:K01047] [EC:3.1.1.4]
122117696  Adm; pro-adrenomedullin [KO:K12333]
122117781  [KO:K12332]
122117843  [KO:K12332]
122117858  Irag1; inositol 1,4,5-triphosphate receptor associated 1 [KO:K12337]
122118832  Calm1; calmodulin-1 [KO:K02183]
122119137  Myh9; myosin-9 [KO:K10352]
122119146  Pla2g6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
122119361  Adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
122119798  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
122120299  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
122120360  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
122120429  Adra1d; alpha-1D adrenergic receptor [KO:K04137]
122120471  [KO:K05242]
122120488  Mylk2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
122120489  Myl9; myosin regulatory light polypeptide 9 [KO:K12755]
122120987  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
122121425  Nppa; natriuretic peptides A [KO:K12334]
122121462  Nppb; natriuretic peptides B [KO:K12335]
122122409  Npr2; atrial natriuretic peptide receptor 2 isoform X1 [KO:K12324] [EC:4.6.1.2]
122122432  Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
122122500  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
122122996  Calml4; calmodulin-like protein 4 isoform X1 [KO:K02183]
122123528  Adra1a; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
122123658  Adm2; protein ADM2 [KO:K25343]
122123709  [KO:K01047] [EC:3.1.1.4]
122123759  Myh11; myosin-11 isoform X1 [KO:K10352]
122123783  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
122124059  [KO:K02183]
122124093  Myl6b; myosin light chain 6B [KO:K12751]
122124094  Myl6; myosin light polypeptide 6 isoform X1 [KO:K12751]
122124245  Kcnmb4; calcium-activated potassium channel subunit beta-4 [KO:K04941]
122124398  Avpr1a; vasopressin V1a receptor [KO:K04226]
122124417  Ppp1r12a; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
122124612  [KO:K04632]
122124614  [KO:K04632]
122124617  Edn3; endothelin-3 [KO:K05227]
122125032  Adra1b; alpha-1B adrenergic receptor [KO:K04136]
122125078  Kcnu1; potassium channel subfamily U member 1 [KO:K05274]
122125164  Actg2; actin, gamma-enteric smooth muscle [KO:K12315]
122125337  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
122125607  Myh14; LOW QUALITY PROTEIN: myosin-14 [KO:K10352]
122125680  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
122125740  Calm3; calmodulin-3 [KO:K02183]
122125823  Ptgir; prostacyclin receptor [KO:K04263]
122126705  Cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
122126861  [KO:K02183]
122127133  Ednra; endothelin-1 receptor [KO:K04197]
122127155  Pla2g12a; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
122128029  Ramp1; receptor activity-modifying protein 1 [KO:K08447]
122128060  Ramp3; receptor activity-modifying protein 3 [KO:K08449]
122128067  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
122128327  Gna13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
122128350  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
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
dsp00590  Arachidonic acid metabolism
dsp04020  Calcium signaling pathway
KO pathway
ko04270   

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