Search results for "INTEGRIN"
showing 10 items of 286 documents
Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2.
2007
Candida albicans is a common opportunistic fungal pathogen and is the leading cause of invasive fungal disease in immunocompromised individuals. The induction of cell-mediated immunity to C. albicans is of critical importance in host defense and the prime task of cells of the innate immune system. We previously demonstrated that the integrin alpha(M)beta(2) (CD11b/CD18) is the major leukocyte receptor involved in C. albicans recognition, mediating both adhesive and migratory responses to the fungus. In the present study, we demonstrate that various C. albicans strains release a protease-sensitive activity into their conditioned medium that supports alpha(M)beta(2)-mediated cell adhesion and…
Differential effects of leflunomide on leukocytes: Inhibition of ratin vivo adhesion and humanin vitro oxidative burst without affecting surface mark…
1994
Leflunomide has been shown to combat effectively autoimmune diseases in a number of animal models, as well as chronic polyarthritis of humans. Here we report on the effects of this novel drug on the adherence of leukocytes to endothelium, an essential event in establishment and maintenance of inflammation. The entry of cells into tissues is dependent on interactions of adhesion molecules. The process of diapedesis, which these molecules control, involves three phases: tethering, triggering of receptors on endothelial cells and firm attachment of leukocytes to these cells. The interaction of LECAM-1 (constitutively expressed on circulating leukocytes) and P- and E-selectins on the vessel wll…
Blockage of collagen binding to integrin α2β1: structure–activity relationship of protein–protein interaction inhibitors
2011
The interaction between the α2β1 integrin and collagen plays a crucial role in the development of pathological conditions, such as thrombus formation and cancer cell metastasis. Accordingly, the α2β1 integrin is a promising target for the development of new drug molecules to treat these diseases. Here, we have designed, synthesized, and measured in vitro a set of novel drug-like compounds that block the protein–protein interactions between α2β1 integrin and collagen. The obtained structure–activity relationship reveals the key features that are required for successful inhibition of this integrin–collagen interaction.
Integrin cytoplasmic domain and pITAM compete for spleen tyrosine kinase binding
2019
ABSTRACTIn hematopoietic tissues cell-cell communication involves immunoreceptors and specialized cell adhesion receptors that both mediate intracellular signals. Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase involved in the downstream signaling of both immunoreceptors tyrosine activation motif (ITAM) receptors and integrin family cell adhesion receptors. Both phosphorylated ITAM (pITAM) and integrins bind to the regulatory domain of Syk composed of two Src homology 2 (SH2) domains. The interaction with pITAM is mediated by binding of a specific phosphotyrosine to each of the SH2 domains, leading to conformational changes and Syk kinase activation. Integrins bind to the int…
The metalloproteinase-disintegrin ADAM10 is exclusively expressed by type I muscle fibers.
2008
ADAM10 (Kuzbanian) is a member of a recently discovered family of membrane-anchored metalloproteinases with a complex and conserved domain structure. In part, these metalloproteinases have been implicated in muscle formation. Herein the expression pattern of ADAM10 in human skeletal muscle was studied. ADAM10 was found to be present in human myoblasts and to be exclusively expressed in type I fibers, suggesting that it may be critical in muscle fiber differentiation.
Entry of Human Parechovirus 1
2001
ABSTRACT Human parechovirus 1 (HPEV-1) is a prototype member of parechoviruses, a recently established picornavirus genus. Although there is preliminary evidence that HPEV-1 recognizes α V integrins as cellular receptors, our understanding of early events during HPEV-1 infection is still very limited. The aim of this study was to clarify the entry mechanisms of HPEV-1, including the attachment of the virus onto the host cell surface and subsequent internalization. In blocking experiments with monoclonal antibodies against different receptor candidates, antibodies against α V and β 3 integrin subunits, in particular in combination, appeared to be the most efficient ones in preventing the HPE…
Structural and functional analysis of integrin alpha2I domain interaction with echovirus 1.
2004
Integrins are cell surface receptors for several microbial pathogens including echovirus 1 (EV1), a picornavirus. Cryo-electron microscopy revealed that the functional domain (alpha(2)I) of human alpha(2)beta(1) integrin binds to a surface depression on the EV1 capsid. This three-dimensional structure of EV1 bound to alpha(2)I domain provides the first structural details of an integrin interacting with a picornavirus. The model indicates that alpha(2)beta(1) integrin cannot simultaneously bind both EV1 and the physiological ligand collagen. Compared with collagen binding to the alpha(2)I domain, the virus binds with a 10-fold higher affinity but in vitro uncoating of EV1 was not observed as…
The Internal Dynamics of Fibrinogen and Its Implications for Coagulation and Adsorption
2015
Fibrinogen is a serum multi-chain protein which, when activated, aggregates to form fibrin, one of the main components of a blood clot. Fibrinolysis controls blood clot dissolution through the action of the enzyme plasmin, which cleaves fibrin at specific locations. Although the main biochemical factors involved in fibrin formation and lysis have been identified, a clear mechanistic picture of how these processes take place is not available yet. This picture would be instrumental, for example, for the design of improved thrombolytic or anti-haemorrhagic strategies, as well as, materials with improved biocompatibility. Here, we present extensive molecular dynamics simulations of fibrinogen w…