Entry Name Leukocyte transendothelial migration - Rhinopithecus bieti (black snub-nosed monkey)
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 systemBRITE hierarchy
Pathway map rbb04670 Leukocyte transendothelial migration
Ortholog table Other DBs Organism Rhinopithecus bieti (black snub-nosed monkey) [GN:
rbb ]
Gene 108518303 JAM2; LOW QUALITY PROTEIN: junctional adhesion molecule B [KO:K06735 ]
108536257 PECAM1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
108516383 ESAM; endothelial cell-selective adhesion molecule isoform X1 [KO:K06787 ]
108544591 PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
108532960 PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
108539355 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
108535636 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
108534276 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
108541175 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
108515883 ras-related C3 botulinum toxin substrate 1-like isoform X1 [KO:K04392 ]
108522897 LOW QUALITY PROTEIN: cytochrome b-245 heavy chain [KO:K21421 ] [EC:1.-.-.-]
108513939 NCF1; LOW QUALITY PROTEIN: neutrophil cytosol factor 1 [KO:K08011 ]
108519825 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
108539491 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
108527422 BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726 ]
108512247 MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
108544023 MYL7; myosin regulatory light chain 2, atrial isoform isoform X1 [KO:K12754 ]
108523051 MYL9; myosin regulatory light polypeptide 9 isoform X1 [KO:K12755 ]
108535399 MYLPF; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758 ]
108542291 SIPA1; signal-induced proliferation-associated protein 1 [KO:K08013 ]
108531097 VASP; LOW QUALITY PROTEIN: vasodilator-stimulated phosphoprotein [KO:K06274 ]
108519632 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
108534866 GNAI1; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
108526962 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
108518542 RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
108535148 RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015 ]
108513251 VAV2; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV2 [KO:K05730 ]
108522647 LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV3-like [KO:K05730 ]
108538451 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
Compound C04637 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
Reference Authors van Buul JD, Hordijk PL.
Title Signaling in leukocyte transendothelial migration.
Journal Reference Authors Wittchen ES, van Buul JD, Burridge K, Worthylake RA.
Title Trading spaces: Rap, Rac, and Rho as architects of transendothelial migration.
Journal Reference 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 Reference Authors Cook-Mills JM, Deem TL.
Title Active participation of endothelial cells in inflammation.
Journal Reference Authors Imhof BA, Aurrand-Lions M.
Title Adhesion mechanisms regulating the migration of monocytes.
Journal Reference 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 Reference 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 Reference Authors Chavakis T, Preissner KT, Santoso S.
Title Leukocyte trans-endothelial migration: JAMs add new pieces to the puzzle.
Journal Reference Authors Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
Title Tec family kinases in T lymphocyte development and function.
Journal Related rbb04810 Regulation of actin cytoskeleton
KO pathway LinkDB All DBs
