KEGG   PATHWAY: cfa04670
Entry
cfa04670                    Pathway                                
Name
Leukocyte transendothelial migration - Canis lupus familiaris (dog)
Description
Leukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (CAM) and then migrate across the vascular endothelium. A leukocyte adherent to CAMs on the endothelial cells moves forward by leading-edge protrusion and retraction of its tail. In this process, alphaL /beta2 integrin activates through Vav1, RhoA, which subsequently activates the kinase p160ROCK. ROCK activation leads to MLC phosphorylation, resulting in retraction of the actin cytoskeleton. Moreover, Leukocytes activate endothelial cell signals that stimulate endothelial cell retraction during localized dissociation of the endothelial cell junctions. ICAM-1-mediated signals activate an endothelial cell calcium flux and PKC, which are required for ICAM-1 dependent leukocyte migration. VCAM-1 is involved in the opening of the "endothelial passage" through which leukocytes can extravasate. In this regard, VCAM-1 ligation induces NADPH oxidase activation and the production of reactive oxygen species (ROS) in a Rac-mediated manner, with subsequent activation of matrix metallopoteinases and loss of VE-cadherin-mediated adhesion.
Class
Organismal Systems; Immune system
Pathway map
cfa04670  Leukocyte transendothelial migration
cfa04670

Other DBs
GO: 0050900
Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
489271  JAM3; junctional adhesion molecule C [KO:K06785]
489928  ITGAM; integrin alpha-M isoform X1 [KO:K06461]
403770  ITGB2; integrin beta-2 isoform X1 [KO:K06464]
488429  ITGA4; integrin alpha-4 isoform X1 [KO:K06483]
477956  ITGB1; integrin beta-1 isoform X1 [KO:K05719]
610775  PECAM1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471]
609832  CD99; CD99 antigen isoform X1 [KO:K06520]
100685328  CD99L2; CD99 antigen-like protein 2 isoform X1 [KO:K06520]
489905  ITGAL; integrin alpha-L isoform X2 [KO:K05718]
478974  F11R; junctional adhesion molecule A [KO:K06089]
489775  CDH5; cadherin-5 [KO:K06533]
608226  CLDN15; claudin-15 isoform X1 [KO:K06087]
490048  CLDN6; claudin-6 [KO:K06087]
490049  CLDN9; claudin-9 [KO:K06087]
487751  CLDN14; claudin-14 [KO:K06087]
403648  CLDN3; claudin-3 [KO:K06087]
477079  CLDN18; claudin-18 isoform X1 [KO:K06087]
403649  CLDN2; claudin-2 [KO:K06087]
489466  CLDN7; claudin-7 [KO:K06087]
478401  CLDN8; claudin-8 [KO:K06087]
476963  CLDN10; claudin-10 isoform X3 [KO:K06087]
608935  CLDN20; claudin-20 [KO:K06087]
488160  CLDN11; claudin-11 [KO:K06087]
487720  CLDN17; claudin-17 [KO:K06087]
482919  claudin-22 [KO:K06087]
608218  CLDN16; claudin-16 isoform X2 [KO:K06087]
608207  CLDN1; claudin-1 [KO:K06087]
100686536  CLDN34; claudin-34 [KO:K06087]
100684266  CLDN5; claudin-5 [KO:K06087]
100687225  CLDN23; claudin-23 [KO:K06087]
100856416  CLDN4; claudin-4 [KO:K06087]
489401  CLDN25; putative claudin-25 [KO:K06087]
482918  CLDN24; putative claudin-24 [KO:K06087]
607005  CLDN19; claudin-19 isoform X2 [KO:K06087]
608397  CLDN12; claudin-12 [KO:K06087]
403844  OCLN; occludin [KO:K06088]
489309  ESAM; endothelial cell-selective adhesion molecule isoform X2 [KO:K06787]
403982  VCAM1; vascular cell adhesion protein 1 precursor [KO:K06527]
484056  EZR; ezrin [KO:K08007]
491924  MSN; moesin isoform X1 [KO:K05763]
403580  ACTB; actin, cytoplasmic 1 [KO:K05692]
475923  ACTG1; actin, cytoplasmic 2 [KO:K05692]
488084  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
489644  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
477085  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
609956  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
487235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100856339  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
403955  RAC1; ras-related C3 botulinum toxin substrate 1 precursor [KO:K04392]
491825  CYBB; cytochrome b-245, beta polypeptide [KO:K21421] [EC:1.-.-.-]
489664  CYBA; cytochrome b-245 alpha chain [KO:K08009]
480036  NCF2; neutrophil cytosol factor 2 [KO:K08010]
607700  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
481277  NCF4; neutrophil cytosol factor 4 isoform X2 [KO:K08012]
477032  CTNNB1; catenin beta-1 [KO:K02105]
483489  CTNND1; catenin delta-1 isoform X1 [KO:K05690]
483088  CTNNA2; catenin alpha-2 isoform X1 [KO:K05691]
489008  CTNNA3; catenin alpha-3 isoform X1 [KO:K05691]
474698  CTNNA1; catenin alpha-1 [KO:K05691]
477488  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100683481  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
403733  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
403885  MMP9; matrix metalloproteinase-9 precursor [KO:K01403] [EC:3.4.24.35]
403856  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
607019  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
607023  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
612821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
403975  ICAM1; intercellular adhesion molecule 1 precursor [KO:K06490]
485874  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
489692  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
490904  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
489968  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100855828  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
475108  PTK2; focal adhesion kinase 1 isoform X14 [KO:K05725] [EC:2.7.10.2]
486299  PXN; paxillin isoform X2 [KO:K05760]
479648  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X9 [KO:K05726]
489365  THY1; thy-1 membrane glycoprotein precursor [KO:K06514]
403543  ARHGAP35; rho GTPase-activating protein 35 [KO:K05732]
490642  ARHGAP5; rho GTPase-activating protein 5 isoform X1 [KO:K13709]
403954  RHOA; transforming protein RhoA [KO:K04513]
480181  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
482970  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
403614  MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351]
479135  MYL5; myosin light chain 5 isoform X1 [KO:K12753]
100683291  MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754]
485856  MYL9; myosin regulatory light polypeptide 9 [KO:K12755]
608177  MYL10; myosin regulatory light chain 10 isoform X2 [KO:K12756]
480193  MYL12B; myosin regulatory light chain 12B [KO:K12757]
607207  myosin regulatory light polypeptide 9 isoform X2 [KO:K12757]
479772  MYLPF; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758]
431695  AFDN; afadin isoform X1 [KO:K05702]
483225  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
608981  RAP1B; ras-related protein Rap-1b [KO:K07836]
483730  SIPA1; signal-induced proliferation-associated protein 1 [KO:K08013]
403936  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
480369  ACTN1; alpha-actinin-1 isoform X2 [KO:K05699]
484526  ACTN4; alpha-actinin-4 isoform X2 [KO:K05699]
479252  VCL; vinculin isoform X14 [KO:K05700]
449622  CXCL12; stromal cell-derived factor 1 isoform 1 precursor [KO:K10031]
119863891  C-X-C chemokine receptor type 4 [KO:K04189]
442957  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
478227  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
611810  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha isoform X2 [KO:K04630]
486591  RAPGEF3; rap guanine nucleotide exchange factor 3 [KO:K08014]
488402  RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X8 [KO:K04351]
607454  RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015]
486102  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
489159  ITK; tyrosine-protein kinase ITK/TSK isoform X1 [KO:K07363] [EC:2.7.10.2]
482139  TXK; tyrosine-protein kinase TXK isoform X1 [KO:K08016] [EC:2.7.10.2]
608060  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
485016  VAV1; proto-oncogene vav isoform X2 [KO:K05730]
479921  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
481271  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
119863888  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
119866928  cell division control protein 42 homolog [KO:K04393]
488833  RHOH; rho-related GTP-binding protein RhoH [KO:K07873]
Compound
C00027  Hydrogen peroxide
C00076  Calcium cation
C00575  3',5'-Cyclic AMP
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Reference
PMID:14976004
  Authors
van Buul JD, Hordijk PL.
  Title
Signaling in leukocyte transendothelial migration.
  Journal
Arterioscler Thromb Vasc Biol 24:824-33 (2004)
DOI:10.1161/01.ATV.0000122854.76267.5c
Reference
PMID:15604886
  Authors
Wittchen ES, van Buul JD, Burridge K, Worthylake RA.
  Title
Trading spaces: Rap, Rac, and Rho as architects of transendothelial migration.
  Journal
Curr Opin Hematol 12:14-21 (2005)
DOI:10.1097/01.moh.0000147892.83713.a7
Reference
PMID:14977592
  Authors
Barreiro O, Vicente-Manzanares M, Urzainqui A, Yanez-Mo M, Sanchez-Madrid F.
  Title
Interactive protrusive structures during leukocyte adhesion and transendothelial migration.
  Journal
Front Biosci 9:1849-63 (2004)
DOI:10.2741/1285
Reference
PMID:15629883
  Authors
Cook-Mills JM, Deem TL.
  Title
Active participation of endothelial cells in inflammation.
  Journal
J Leukoc Biol 77:487-95 (2005)
DOI:10.1189/jlb.0904554
Reference
PMID:15173832
  Authors
Imhof BA, Aurrand-Lions M.
  Title
Adhesion mechanisms regulating the migration of monocytes.
  Journal
Nat Rev Immunol 4:432-44 (2004)
DOI:10.1038/nri1375
Reference
PMID:15265790
  Authors
Deem TL, Cook-Mills JM.
  Title
Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species.
  Journal
Blood 104:2385-93 (2004)
DOI:10.1182/blood-2004-02-0665
Reference
PMID:10975856
  Authors
Etienne-Manneville S, Manneville JB, Adamson P, Wilbourn B, Greenwood J, Couraud PO.
  Title
ICAM-1-coupled cytoskeletal rearrangements and transendothelial lymphocyte migration involve intracellular calcium signaling in brain endothelial cell lines.
  Journal
J Immunol 165:3375-83 (2000)
DOI:10.4049/jimmunol.165.6.3375
Reference
PMID:12540948
  Authors
Chavakis T, Preissner KT, Santoso S.
  Title
Leukocyte trans-endothelial migration: JAMs add new pieces to the puzzle.
  Journal
Thromb Haemost 89:13-7 (2003)
DOI:10.1055/s-0037-1613537
Reference
PMID:15771581
  Authors
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
  Title
Tec family kinases in T lymphocyte development and function.
  Journal
Annu Rev Immunol 23:549-600 (2005)
DOI:10.1146/annurev.immunol.22.012703.104743
Related
pathway
cfa04514  Cell adhesion molecules
cfa04810  Regulation of actin cytoskeleton
KO pathway
ko04670   

  All links  
Genome (1)   
   KEGG GENOME (1)   
Gene (116)   
   KEGG GENES (116)   
All databases (117)   

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