Identifiers
NAME:ITGAV:ITGB3
References
PMID:19449109
Identifiers
NAME:ITGAV:ITGB3
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:8636223
Integrin aVb3 is distinct in its capacity to recognize the sequence Arg-Gly-Asp (RGD) in many extra-cellular matrix (ECM) components.
aVb3 can also interact with the neural cell adhesion molecule L1CAM; a member of the immunoglobulin superfamily (IgSF). In other words, aVb3 undergoes heterophilic binding with L1CAM
M21 cells display some aVb3-dependent adhesion and spreading on immunopurified human L1. Ligation between this ligand and aVb3 was also observed to promote significant haptotactic cell migration.
Significant aVb3-dependent adhesion and spreading was evident on a L1 fragment containing Ig-like domains 4, 5, and 6.
Importantly, mutation of an RGD sequence present in the sixth Ig-like domain of L1 abrogated M21 cell adhesion.
Despite high levels of L1 expression the M21 melanoma cells did not display significant adhesion via a homophilic L1-L1 interaction.
These data suggest that M21 melanoma cells recognize and adhere to L1 through a mechanism that is primarily heterophilic and integrin dependent.
Finally, we present evidence that melanoma cells can shed and deposit L1 in occluding ECM.
aVb3 may recognize L1 in a cell-cell or cell-substrate interaction.
PMID:11553709
Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin aVb3 has been associated with the metastatic potential of tumor cells.
In the context of in vitro monolayer of human lung microvascular, L1CAM was shown to serve as a potential ligand for aVb3 during melanoma transendothelial migration.
Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells.
However, addition of both L1 and aVb3 antibodies did not show additive effects, suggesting that they are components of the same adhesion system.
Together, the data suggest that interactions between the integrin aVb3 on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.
PMID:10022831
Interaction between integrin avb3 and extracellular matrix,as the most important survival system for nascent vessels, is crucial for endothelial cells sprouting from capillaries and for angiogenesis.
Tyrosine-phosphorylated VEGFR2 co-immunoprecipitated with b3 integrin subunit, but not with b1 or b5, from cells stimulated with VEGFA (165 amino acid isoform)
VEGFR2 phosphorylation and mitogenicity induced by VEGFA were enhanced in cells plated on the avb3 ligand, vitronectin, compared with cells plated on the a5b1 ligand, fibronectin or the a2b1 ligand, collagen.
A new role for avb3 integrin in the activation of an in vitro angiogenic program in endothelial cells.
Besides being the most important survival system for nascent vessels by regulating cell adhesion to matrix, avb3 integrin participates in the full activation of VEGFR2 triggered by VEGFA.
PMID:7512751
PMID:8755653
Integrin avb3 is expressed in high quantities on angiogenic endothelial cells where it suppresses the activity of p53 and the p53-inducible cell-cycle inhibitor p21WAF1/CIP1 and increases the BCL2/Bax ratio, with a consequent antiapoptotic effect
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
Integrins control motile strategy through a Rho-cofilin pathway.
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.
Identifiers
NAME:ITGAV:ITGB3
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Innate Immunity / DANGER_SIGNAL_PATHWAYS
Innate Immunity / INTEGRINS
References
CASCADE:INTEGRIN_AVB3
DENDRITIC_CELL
PMID:9295024, PMID:9763615
Dendritic cells phagocytose apoptotic cells via alphavbeta5, alphavbeta3, and CD36.
and cross-present Antigens to Cytotoxic T Lymphocytes
The interaction between apoptotic bodies and dendritic cells elicits a rise in intracellular free calcium concentration ([Ca2+]i) which is essential for the process of engulfment.
+ FAK*@Cytosol → FAK*:ITGAV:ITGB3@Cytosol
→ ITGAV:ITGB3@Cytosol
→ ITGAV:ITGB3@Cytosol
+ ITGB3@Cytosol → ITGAV:ITGB3@Cytosol
→ ITGAV:ITGB3@Cytosol
+ ITGAV:ITGB3@Cytosol → em_emtc_emtc_s3594
→ Angiogenesis@Nucleus
→ ITGAV:ITGB3@Cytosol
→ ITGAV:ITGB3@Cytosol
→ (ITGAV:ITGB3)|active@Extracellular space
+ MFGE8@TUMOR_CELL_AS_INDUCTOR_Membrane + ITGAV:ITGB3@INNATE_IMMUNE_CELL_Membrane → ITGAV:ITGB3:MFGE8:PtdSer@INNATE_IMMUNE_CELL_Membrane