Entry Name Leukocyte transendothelial migration - Peromyscus leucopus (white-footed mouse)
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 pleu04670 Leukocyte transendothelial migration
Other DBs Organism Peromyscus leucopus (white-footed mouse) [GN:
pleu ]
Gene 114682105 Sipa1; LOW QUALITY PROTEIN: signal-induced proliferation-associated protein 1 [KO:K08013 ]
114684032 Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114684216 Vav2; guanine nucleotide exchange factor VAV2 isoform X4 [KO:K05730 ]
114688966 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
114690420 Pecam1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
114693559 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114694098 Myl7; myosin regulatory light chain 2, atrial isoform isoform X1 [KO:K12754 ]
114695335 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
114697206 Cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
114698056 Rassf5; LOW QUALITY PROTEIN: ras association domain-containing protein 5 [KO:K08015 ]
114699957 Vav3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730 ]
114699988 Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
114703850 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
114704363 Mylpf; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758 ]
114704477 Rapgef4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
114706924 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
114707535 Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
114708228 Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
114709099 Bcar1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726 ]
114710330 Myl10; LOW QUALITY PROTEIN: myosin regulatory light chain 10 [KO:K12756 ]
114710969 Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [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 pleu04514 Cell adhesion molecule (CAM) interaction
KO pathway
