KEGG   PATHWAY: mlx04270
Entry
mlx04270                    Pathway                                
Name
Vascular smooth muscle contraction - Mirounga leonina (Southern elephant seal)
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
mlx04270  Vascular smooth muscle contraction
mlx04270

Other DBs
GO: 0014829
Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
117997416  EDN1; endothelin-1 isoform X1 [KO:K16366]
117997738  ADM2; protein ADM2 [KO:K25343]
117997778  PPP1R12C; protein phosphatase 1 regulatory subunit 12C isoform X1 [KO:K17457]
117997993  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
117998070  ARHGEF1; rho guanine nucleotide exchange factor 1 isoform X1 [KO:K12330]
117998176  CALM3; calmodulin-3 [KO:K02183]
117998177  PTGIR; prostacyclin receptor isoform X1 [KO:K04263]
117998259  MYH14; myosin-14 isoform X1 [KO:K10352]
117998687  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
117998736  MYH9; myosin-9 [KO:K10352]
117999123  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
117999301  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
117999637  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999826  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999859  ADORA2A; adenosine receptor A2a [KO:K04266]
118000061  MYH10; myosin-10 [KO:K10352]
118000116  ADORA2B; adenosine receptor A2b [KO:K04267]
118001326  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
118002020  PRKCH; protein kinase C eta type isoform X1 [KO:K18051] [EC:2.7.11.13]
118002566  CALM1; calmodulin-1 [KO:K02183]
118003092  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118003137  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
118003270  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
118003295  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
118003336  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118003418  [KO:K16342] [EC:3.1.1.4]
118003546  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
118003693  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
118003869  [KO:K12332]
118004038  IRAG1; protein MRVI1 isoform X1 [KO:K12337]
118004144  ADM; ADM isoform X1 [KO:K12333]
118004318  [KO:K12332]
118004574  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
118004882  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
118004937  AGTR1; type-1 angiotensin II receptor [KO:K04166]
118005070  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
118005176  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
118005236  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
118005431  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118005532  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
118005670  RHOA; transforming protein RhoA [KO:K04513]
118006050  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
118006264  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
118006519  KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938]
118006603  KCNMB3; LOW QUALITY PROTEIN: calcium-activated potassium channel subunit beta-3 [KO:K04939]
118007012  MYLK; LOW QUALITY PROTEIN: myosin light chain kinase, smooth muscle [KO:K00907] [EC:2.7.11.18]
118007016  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
118007595  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
118007652  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
118007723  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
118007966  ACTG2; actin, gamma-enteric smooth muscle [KO:K12315]
118008161  CALM2; calmodulin-2 [KO:K02183]
118008176  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
118008531  PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270]
118008570  KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941]
118008633  AVPR1A; vasopressin V1a receptor [KO:K04226]
118008720  MYL6B; myosin light chain 6B [KO:K12751]
118008722  MYL6; myosin light polypeptide 6 isoform X1 [KO:K12751]
118008901  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
118008972  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
118009788  KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274]
118009801  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
118011101  AVP; vasopressin-neurophysin 2-copeptin [KO:K05242]
118011244  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011247  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118011279  ADRA1D; alpha-1D adrenergic receptor [KO:K04137]
118011350  MYLK2; myosin light chain kinase 2, skeletal/cardiac muscle [KO:K00907] [EC:2.7.11.18]
118011444  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
118011724  NPPC; C-type natriuretic peptide [KO:K12336]
118011898  RAMP1; receptor activity-modifying protein 1 isoform X1 [KO:K08447]
118012234  CALCRL; calcitonin gene-related peptide type 1 receptor [KO:K04577]
118012486  [KO:K02183]
118012894  AGT; angiotensinogen [KO:K09821]
118012959  ACTA2; actin, aortic smooth muscle [KO:K12313]
118012977  PRKG1; cGMP-dependent protein kinase 1 isoform X1 [KO:K07376] [EC:2.7.11.12]
118013176  GUCY1A2; guanylate cyclase soluble subunit alpha-2 isoform X1 [KO:K12318] [EC:4.6.1.2]
118013325  ARHGEF12; rho guanine nucleotide exchange factor 12 isoform X1 [KO:K07532]
118013664  AVPR1B; vasopressin V1b receptor [KO:K04227]
118013821  NPR1; atrial natriuretic peptide receptor 1 isoform X1 [KO:K12323] [EC:4.6.1.2]
118013935  ARHGEF11; rho guanine nucleotide exchange factor 11 [KO:K12331]
118014193  PPP1R12B; protein phosphatase 1 regulatory subunit 12B isoform X1 [KO:K12329]
118014221  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
118014408  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
118015219  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
118015997  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118016125  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
118016156  ADRA1B; alpha-1B adrenergic receptor [KO:K04136]
118016201  [KO:K12332]
118016596  [KO:K02183]
118016627  KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937]
118017958  NPR2; atrial natriuretic peptide receptor 2 isoform X1 [KO:K12324] [EC:4.6.1.2]
118018468  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
118018542  PLA2G1B; phospholipase A2 [KO:K01047] [EC:3.1.1.4]
118018703  PLA2G3; group 3 secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
118019227  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
118019612  EDN2; endothelin-2 [KO:K16367]
118019636  PLA2G2C; LOW QUALITY PROTEIN: putative inactive group IIC secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
118019658  CALML6; calmodulin-like protein 6 [KO:K02183]
118020315  PLA2G2F; group IIF secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
118020316  [KO:K01047] [EC:3.1.1.4]
118020317  [KO:K01047] [EC:3.1.1.4]
118020318  [KO:K01047] [EC:3.1.1.4]
118020337  NPPB; natriuretic peptides B [KO:K12335]
118020338  NPPA; natriuretic peptides A [KO:K12334]
118020691  [KO:K02183]
118021115  CALD1; caldesmon isoform X1 [KO:K12327]
118021159  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
118021504  PLA2G12B; group XIIB secretory phospholipase A2-like protein isoform X1 [KO:K01047] [EC:3.1.1.4]
118021606  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
118021620  CALML3; calmodulin-like protein 3 [KO:K02183]
118021775  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
118021860  MYH11; myosin-11 isoform X1 [KO:K10352]
118021903  [KO:K02183]
118021946  [KO:K01047] [EC:3.1.1.4]
118022052  KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936]
118022108  ADRA1A; alpha-1A adrenergic receptor isoform X1 [KO:K04135]
118022213  GUCY1B1; guanylate cyclase soluble subunit beta-1 isoform X1 [KO:K12319] [EC:4.6.1.2]
118022214  GUCY1A1; guanylate cyclase soluble subunit alpha-1 [KO:K12318] [EC:4.6.1.2]
118022264  EDNRA; endothelin-1 receptor [KO:K04197]
118022704  PPP1R14A; protein phosphatase 1 regulatory subunit 14A [KO:K12328]
118023087  [KO:K04632]
118023800  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
118023826  MYLK3; myosin light chain kinase 3 isoform X1 [KO:K00907] [EC:2.7.11.18]
118024008  [KO:K04632]
118024010  [KO:K04632]
118024108  EDN3; endothelin-3 [KO:K05227]
118024340  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
118024347  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
118024512  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
118024580  RAMP3; receptor activity-modifying protein 3 [KO:K08449]
118024932  RAMP2; receptor activity-modifying protein 2 isoform X1 [KO:K08448]
118025560  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
118025809  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
118026266  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
118027088  PLA2G12A; group XIIA secretory phospholipase A2 [KO:K01047] [EC:3.1.1.4]
118027388  MYLK4; myosin light chain kinase family member 4 isoform X1 [KO:K00907] [EC:2.7.11.18]
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
mlx00590  Arachidonic acid metabolism
mlx04020  Calcium signaling pathway
KO pathway
ko04270   

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