Entry Name Leukocyte transendothelial migration - Mus musculus (house 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 mmu04670 Leukocyte transendothelial migration
Ortholog table Other DBs Organism Mus musculus (house mouse) [GN:
mmu ]
Gene 16412 Itgb1; integrin beta 1 (fibronectin receptor beta) [KO:K05719 ]
18613 Pecam1; platelet/endothelial cell adhesion molecule 1 [KO:K06471 ]
69524 Esam; endothelial cell-specific adhesion molecule [KO:K06787 ]
22329 Vcam1; vascular cell adhesion molecule 1 [KO:K06527 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
13058 Cybb; cytochrome b-245, beta polypeptide [KO:K21421 ] [EC:1.-.-.-]
13057 Cyba; cytochrome b-245, alpha polypeptide [KO:K08009 ]
15894 Icam1; intercellular adhesion molecule 1 [KO:K06490 ]
12927 Bcar1; breast cancer anti-estrogen resistance 1 [KO:K05726 ]
232906 Arhgap35; Rho GTPase activating protein 35 [KO:K05732 ]
11855 Arhgap5; Rho GTPase activating protein 5 [KO:K13709 ]
67653 4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513 ]
17906 Myl2; myosin, light polypeptide 2, regulatory, cardiac, slow [KO:K10351 ]
17898 Myl7; myosin, light polypeptide 7, regulatory [KO:K12754 ]
98932 Myl9; myosin, light polypeptide 9, regulatory [KO:K12755 ]
59310 Myl10; myosin, light chain 10, regulatory [KO:K12756 ]
67938 Myl12b; myosin, light chain 12B, regulatory [KO:K12757 ]
67268 Myl12a; myosin, light chain 12A, regulatory, non-sarcomeric [KO:K12757 ]
17907 Mylpf; myosin light chain, phosphorylatable, fast skeletal muscle [KO:K12758 ]
17356 Afdn; afadin, adherens junction formation factor [KO:K05702 ]
20469 Sipa1; signal-induced proliferation associated gene 1 [KO:K08013 ]
22323 Vasp; vasodilator-stimulated phosphoprotein [KO:K06274 ]
20315 Cxcl12; C-X-C motif chemokine ligand 12 [KO:K10031 ]
12767 Cxcr4; C-X-C motif chemokine receptor 4 [KO:K04189 ]
223864 Rapgef3; Rap guanine nucleotide exchange factor (GEF) 3 [KO:K08014 ]
56508 Rapgef4; Rap guanine nucleotide exchange factor (GEF) 4 [KO:K04351 ]
54354 Rassf5; Ras association (RalGDS/AF-6) domain family member 5 [KO:K08015 ]
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 mmu04810 Regulation of actin cytoskeleton
KO pathway LinkDB All DBs
