Entry Name Leukocyte transendothelial migration - Ailuropoda melanoleuca (giant panda)
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 aml04670 Leukocyte transendothelial migration
Other DBs Organism Ailuropoda melanoleuca (giant panda) [GN:
aml ]
Gene 100463775 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100465076 CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
100466105 ESAM; LOW QUALITY PROTEIN: endothelial cell-selective adhesion molecule [KO:K06787 ]
100466408 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
100467916 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
100471767 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
100473947 RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014 ]
100474217 PECAM1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
100475291 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100475493 MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754 ]
100478770 VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274 ]
100479294 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100479448 BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X2 [KO:K05726 ]
100479580 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
100480097 RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
100480191 MYLPF; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758 ]
100480409 SIPA1; signal-induced proliferation-associated protein 1 [KO:K08013 ]
100480586 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116 ] [EC:3.1.4.11 ]
100481994 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
100483724 MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
100483828 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
100484933 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
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 aml04810 Regulation of actin cytoskeleton
KO pathway
