Entry Name Leukocyte transendothelial migration - Phascolarctos cinereus (koala)
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 pcw04670 Leukocyte transendothelial migration
Other DBs Organism Phascolarctos cinereus (koala) [GN:
pcw ]
Gene 110192462 BCAR1; LOW QUALITY PROTEIN: breast cancer anti-estrogen resistance protein 1 [KO:K05726 ]
110193513 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
110195560 SIPA1; signal-induced proliferation-associated protein 1 [KO:K08013 ]
110195824 JAM3; LOW QUALITY PROTEIN: junctional adhesion molecule C [KO:K06785 ]
110196868 MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
110199476 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
110201486 RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014 ]
110203322 VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274 ]
110204454 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
110205369 VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730 ]
110206033 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
110206410 MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754 ]
110206959 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
110208219 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110209293 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
110211578 RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
110216530 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
110216705 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
110216929 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
110217531 VCAM1; LOW QUALITY PROTEIN: vascular cell adhesion protein 1 [KO:K06527 ]
110218202 PECAM1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
110218213 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha isoform X1 [KO:K04630 ]
110223139 MYLPF; myosin regulatory light chain 2, skeletal muscle isoform isoform X1 [KO:K12758 ]
110223395 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
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 pcw04810 Regulation of actin cytoskeleton
KO pathway
