Entry Name Leukocyte transendothelial migration - Mus pahari (shrew 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 mpah04670 Leukocyte transendothelial migration
Other DBs Organism Mus pahari (shrew mouse) [GN:
mpah ]
Gene 110312960 Myl2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
110317622 Vav2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730 ]
110318312 Myl9; myosin regulatory light polypeptide 9 isoform X1 [KO:K12755 ]
110318780 Rapgef4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
110319649 Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
110319750 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110319821 Gnai3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
110319846 Vav3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730 ]
110322688 Rassf5; ras association domain-containing protein 5 isoform X1 [KO:K08015 ]
110322847 Cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393 ]
110322865 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
110323448 Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110323777 Sipa1; signal-induced proliferation-associated protein 1 [KO:K08013 ]
110325851 Mylpf; myosin regulatory light chain 2, skeletal muscle isoform isoform X1 [KO:K12758 ]
110327202 Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
110327251 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
110328811 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
110330683 Myl7; myosin regulatory light chain 2, atrial isoform [KO:K12754 ]
110331583 Pecam1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
110334678 Rac2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
110334708 Rapgef3; rap guanine nucleotide exchange factor 3 isoform X1 [KO:K08014 ]
110336413 Vasp; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274 ]
110336420 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
110337447 Bcar1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726 ]
110339030 Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
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 KO pathway
