Identifiers
NAME:ITGA5:ITGB1
References
PMID:16076871
Identifiers
NAME:ITGA5:ITGB1
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / INTEGRINS
References
NATURAL_KILLER
CASCADE:INTEGRIN_A5B1
PMID:9973479
Beta 1 integrin cross-linking inhibits CD16-induced phospholipase D and secretory phospholipase A2 activity and granule exocytosis in human NK cells.
Identifiers
NAME:ITGA5:ITGB1
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / ECM
EMT Senescence / CELL_MATRIX_ADHESIONS
References
PMID:19161977
In the endoplasmic reticulum, integrin subunits find their binding partners and form heterodimers.
Monomeric integrins never reach the cell surface.
PMID:19487819
During gastrulation, type 1 EMT is associated with de novo expression of a5b1, which is a receptor for fibronectin.
Type 2 EMT in experimental kidney fibrosis is associated with increased a5 integrin expression.
em_emtc_emtc_re471( EMT Senescence ):
PMID:22154077, PMID:17522712
CDC42 promotes changes in actin cytoskeleton by several pathways.
PMID:10461188
PMID:11950587
PMID:11340065
PMID:10559936
PMID:10613909
PMID:11413130
CDC42 activates PAK1,2,3,4 and CDC42BPA (MRCKalpha) which phosphorylate LIMK1,2.
LIMK1,2 subsquently phosphorylate and inhibit Cofilin
Destrin as actin depolymerizing factor, once phosphorylated by LIMK1,2 is inactive and thus this phosphorylation leads to actin polymerization and stimulation of filopodia and stress fibers formation.
PMID:15866889
The ARP2_3 complex and Cofilin are involved in protrusion at the leading edge: the actin-severing activity of cofilin and the actin-branching activity of Arp2_3 act in synergy to drive the extension of lamellipodia.
Cofilin is also required for the maintenance of a polarized cytoskeleton and thus for directional cell migration.
Integrins control motile strategy through a Rho-cofilin pathway.
Adhesion to fibronectin by a5b1 integrin leads to phosphorylation and thus inactivation of cofilin.
Cells thus fail to polarize their cytoskeleton but extend thin protrusion with cell-matrix adhesions in multiple directions.
em_emtc_emtc_re978( EMT Senescence ):
Autophosphorylation of PTK2:
PMID:7529872
PMID:19339212
PMID:7657702
PMID:16919435
FAK (PTK2) is first recruited to sites of integrin clustering via interactions wiith integrin-associated proteins such as talin, paxillin.
FAK binds to the cytoplasmic domain of b1 integrin via Paxillin (PXN) and Talin (TLN)
Binding to aVb3 or a5b1 integrins induces PTK2 (FAK1) autophosphorylation at Y397.
PMID:10545505
FAK associates with paxillin, vinculin, and p130cas (BCAR1) in the focal adhesion complex
beta1 integrins promote random migration, whereas beta3 integrins promote persistent migration in the same epithelial cell background.
Adhesion to fibronectin by aVb3 supports actin cytoskeletal reorganization via cofilin, resulting in a single broad lamellipod with static cell-matrix adhesions at the leading edge.
Adhesion by a5b1 instead leads to the phosphorylation and thus inactivation of cofilin, and these cells fail to polarize their cytoskeleton but extend thin protrusions containing highly dynamic cell-matrix adhesions in multiple directions.
The activity of the small GTPase RhoA is particularly high in cells adhering by a5b1, and inhibition of Rho signaling causes a switch from a beta1 to a beta3-associated mode of migration, whereas increased Rho activity has the opposite effect.
Alterations in integrin expression profiles thus allow cells to modulate several critical aspects of the motile machinery through Rho GTPases.
→ ITGA5:ITGB1@Cytosol
+ ITGB1@Cytosol → ITGA5:ITGB1@Cytosol
→ ITGA5:ITGB1@Cytosol
→ ITGA5:ITGB1@Cytosol
→ (ITGA5:ITGB1)|active@Extracellular space
+ ITGA5:ITGB1@INNATE_IMMUNE_CELL_Membrane → FN1:ITGA5:ITGB1@INNATE_IMMUNE_CELL_Membrane
+ ITGA5@INNATE_IMMUNE_CELL_Membrane → ITGA5:ITGB1@INNATE_IMMUNE_CELL_Membrane