Entry Name Leukocyte transendothelial migration - Macaca mulatta (rhesus monkey)
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 mcc04670 Leukocyte transendothelial migration
Ortholog table Other DBs Organism Macaca mulatta (rhesus monkey) [GN:
mcc ]
Gene 718302 PECAM1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
708996 CD99L2; CD99 antigen-like protein 2 precursor [KO:K06520 ]
719824 F11R; junctional adhesion molecule A precursor [KO:K06089 ]
712200 ESAM; endothelial cell-selective adhesion molecule precursor [KO:K06787 ]
716098 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
709959 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
710552 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
707310 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
719367 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
698996 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649 ]
717755 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
696542 CYBB; cytochrome b-245 heavy chain [KO:K21421 ] [EC:1.-.-.-]
715052 NCF2; neutrophil cytosol factor 2 isoform X1 [KO:K08010 ]
695612 NCF4; neutrophil cytosol factor 4 isoform X1 [KO:K08012 ]
712280 ICAM1; intercellular adhesion molecule 1 precursor [KO:K06490 ]
697069 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
714173 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859 ] [EC:3.1.4.11 ]
713965 BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726 ]
705321 THY1; thy-1 membrane glycoprotein precursor [KO:K06514 ]
716936 ARHGAP35; rho GTPase-activating protein 35 [KO:K05732 ]
711937 MYL2; myosin regulatory light chain 2, ventricular/cardiac muscle isoform [KO:K10351 ]
707293 MYL7; myosin regulatory light chain 2, atrial isoform [KO:K12754 ]
709784 MYL9; myosin regulatory light polypeptide 9 [KO:K12755 ]
694957 MYL12B; myosin regulatory light chain 12B [KO:K12757 ]
695077 MYL12A; myosin, light chain 12A, regulatory, non-sarcomeric isoform X1 [KO:K12757 ]
711778 MYLPF; myosin regulatory light chain 2, skeletal muscle isoform [KO:K12758 ]
693750 LOW QUALITY PROTEIN: ras-related protein Rap-1b [KO:K07836 ]
715958 SIPA1; signal-induced proliferation-associated protein 1 isoform X1 [KO:K08013 ]
716022 VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274 ]
574334 CXCL12; stromal cell-derived factor 1 precursor [KO:K10031 ]
699310 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
703780 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
708940 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630 ]
703967 RAPGEF3; rap guanine nucleotide exchange factor 3 isoform X2 [KO:K08014 ]
698148 RAPGEF4; rap guanine nucleotide exchange factor 4 isoform X1 [KO:K04351 ]
695382 RASSF5; ras association domain-containing protein 5 isoform X1 [KO:K08015 ]
694685 VAV3; guanine nucleotide exchange factor VAV3 isoform X2 [KO:K05730 ]
713227 VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730 ]
696709 RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860 ]
707637 CDC42; cell division control protein 42 homolog [KO:K04393 ]
700499 RHOH; rho-related GTP-binding protein RhoH [KO:K07873 ]
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 mcc04810 Regulation of actin cytoskeleton
KO pathway LinkDB All DBs
