Entry Name Leukocyte transendothelial migration - Ictidomys tridecemlineatus (thirteen-lined ground squirrel)
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 iti04670 Leukocyte transendothelial migration
Other DBs Organism Ictidomys tridecemlineatus (thirteen-lined ground squirrel) [GN:
iti ]
Gene 101954993 Mylpf; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758 ]
101955670 Rapgef4; LOW QUALITY PROTEIN: rap guanine nucleotide exchange factor 4 [KO:K04351 ]
101957854 Gnai3; guanine nucleotide-binding protein G(i) subunit alpha-3 isoform X1 [KO:K04630 ]
101958250 Myl7; myosin regulatory light chain 2, atrial isoform [KO:K12754 ]
101958429 Vav2; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV2 [KO:K05730 ]
101959100 Cdc42; cell division control protein 42 homolog isoform X2 [KO:K04393 ]
101959882 Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
101962360 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101964238 Esam; endothelial cell-selective adhesion molecule isoform X1 [KO:K06787 ]
101964684 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
101964713 Bcar1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726 ]
101966625 Myl2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
101967121 Sipa1; signal-induced proliferation-associated protein 1 [KO:K08013 ]
101970750 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
101972903 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
101974200 Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
101976353 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101976732 Pecam1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
101977192 Rassf5; ras association domain-containing protein 5 isoform X2 [KO:K08015 ]
101977694 Vav3; guanine nucleotide exchange factor VAV3 isoform X2 [KO:K05730 ]
101978230 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
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 iti04810 Regulation of actin cytoskeleton
KO pathway
