Integrins. Medical search

A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.

Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)

Adherence of cells to surfaces or to other cells.

An alpha integrin with a molecular weight of 160-kDa that is found in a variety of cell types. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds. Integrin alphaV can combine with several different beta subunits to form heterodimers that generally bind to RGD sequence-containing extracellular matrix proteins.

Cell-surface glycoprotein beta-chains that are non-covalently linked to specific alpha-chains of the CD11 family of leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE-ADHESION). A defect in the gene encoding CD18 causes LEUKOCYTE-ADHESION DEFICIENCY SYNDROME.

Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.

Receptors such as INTEGRIN ALPHAVBETA3 that bind VITRONECTIN with high affinity and play a role in cell migration. They also bind FIBRINOGEN; VON WILLEBRAND FACTOR; osteopontin; and THROMBOSPONDINS.

An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.

An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.

An integrin that binds to a variety of plasma and extracellular matrix proteins containing the conserved RGD amino acid sequence and modulates cell adhesion. Integrin alphavbeta3 is highly expressed in OSTEOCLASTS where it may play role in BONE RESORPTION. It is also abundant in vascular smooth muscle and endothelial cells, and in some tumor cells, where it is involved in angiogenesis and cell migration. Although often referred to as the vitronectin receptor there is more than one receptor for vitronectin (RECEPTORS, VITRONECTIN).

Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins.

Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.

A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.

Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.

Specific cell surface receptors which bind to FIBRONECTINS. Studies have shown that these receptors function in certain types of adhesive contact as well as playing a major role in matrix assembly. These receptors include the traditional fibronectin receptor, also called INTEGRIN ALPHA5BETA1 and several other integrins.

An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.

The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.

This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.

A blood plasma glycoprotein that mediates cell adhesion and interacts with proteins of the complement, coagulation, and fibrinolytic cascade. (From Segen, Dictionary of Modern Medicine, 1992)

The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.

An integrin alpha subunit that occurs as alternatively spliced isoforms. The isoforms are differentially expressed in specific cell types and at specific developmental stages. Integrin alpha3 combines with INTEGRIN BETA1 to form INTEGRIN ALPHA3BETA1 which is a heterodimer found primarily in epithelial cells.

Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.

A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.

Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.

An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.

A 235-kDa cytoplasmic protein that is also found in platelets. It has been localized to regions of cell-substrate adhesion. It binds to INTEGRINS; VINCULIN; and ACTINS and appears to participate in generating a transmembrane connection between the extracellular matrix and the cytoskeleton.

Peptides composed of between two and twelve amino acids.

Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.

Collagen receptors are cell surface receptors that modulate signal transduction between cells and the EXTRACELLULAR MATRIX. They are found in many cell types and are involved in the maintenance and regulation of cell shape and behavior, including PLATELET ACTIVATION and aggregation, through many different signaling pathways and differences in their affinities for collagen isoforms. Collagen receptors include discoidin domain receptors, INTEGRINS, and glycoprotein VI.

An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (ANTIGENS, CD18) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.

An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.

An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.

Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

An integrin alpha subunit that primarily combines with INTEGRIN BETA1 to form the INTEGRIN ALPHA2BETA1 heterodimer. It contains a domain which has homology to collagen-binding domains found in von Willebrand factor.

A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.

Cell surface glycoproteins on lymphocytes and other leukocytes that mediate adhesion to specialized blood vessels called high endothelial venules. Several different classes of lymphocyte homing receptors have been identified, and they appear to target different surface molecules (addressins) on high endothelial venules in different tissues. The adhesion plays a crucial role in the trafficking of lymphocytes.

Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).

A family of non-receptor, PROLINE-rich protein-tyrosine kinases.

Tetraspanin proteins found associated with LAMININ-binding INTEGRINS. The CD151 antigens may play a role in the regulation of CELL MOTILITY.

This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

Antibodies produced by a single clone of cells.

A group of INTEGRINS that includes the platelet outer membrane glycoprotein GPIIb-IIIa (PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX) and the vitronectin receptor (RECEPTORS, VITRONECTIN). They play a major role in cell adhesion and serve as receptors for fibronectin, von Willebrand factor, and vitronectin.

A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.

An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of the ACTIN CYTOSKELETON terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.

A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)

An alpha-integrin subunit found on lymphocytes, granulocytes, macrophages and monocytes. It combines with the integrin beta2 subunit (CD18 ANTIGEN) to form LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1.

Also known as CD104 antigen, this protein is distinguished from other beta integrins by its relatively long cytoplasmic domain (approximately 1000 amino acids vs. approximately 50). Five alternatively spliced isoforms have been described.

Members of the integrin family appearing late after T-cell activation. They are a family of proteins initially identified at the surface of stimulated T-cells, but now identified on a variety of cell types. At least six VLA antigens have been identified as heterodimeric adhesion receptors consisting of a single common beta-subunit and different alpha-subunits.

The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.

A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).

Glycoprotein molecules on the surface of cells that react with or bind to laminin whose function allows the binding of epithelial cells to the basement membrane. The molecular weight of this high-affinity receptor is 67 kD.

Established cell cultures that have the potential to propagate indefinitely.

Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

A major adhesion-associated heterodimer molecule expressed by MONOCYTES; GRANULOCYTES; NK CELLS; and some LYMPHOCYTES. The alpha subunit is the CD11C ANTIGEN, a surface antigen expressed on some myeloid cells. The beta subunit is the CD18 ANTIGEN.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Family of proteins associated with the capacity of LEUKOCYTES to adhere to each other and to certain substrata, e.g., the C3bi component of complement. Members of this family are the LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; (LFA-1), the MACROPHAGE-1 ANTIGEN; (Mac-1), and the INTEGRIN ALPHAXBETA2 or p150,95 leukocyte adhesion protein. They all share a common beta-subunit which is the CD18 antigen. All three of the above antigens are absent in inherited LEUKOCYTE-ADHESION DEFICIENCY SYNDROME, which is characterized by recurrent bacterial infections, impaired pus formation, and wound healing as well as abnormalities in a wide spectrum of adherence-dependent functions of granulocytes, monocytes, and lymphoid cells.

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

Platelet membrane glycoprotein complex important for platelet adhesion and aggregation. It is an integrin complex containing INTEGRIN ALPHAIIB and INTEGRIN BETA3 which recognizes the arginine-glycine-aspartic acid (RGD) sequence present on several adhesive proteins. As such, it is a receptor for FIBRINOGEN; VON WILLEBRAND FACTOR; FIBRONECTIN; VITRONECTIN; and THROMBOSPONDINS. A deficiency of GPIIb-IIIa results in GLANZMANN THROMBASTHENIA.

Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.

Rare, autosomal recessive disorder caused by deficiency of the beta 2 integrin receptors (RECEPTORS, LEUKOCYTE-ADHESION) comprising the CD11/CD18 family of glycoproteins. The syndrome is characterized by abnormal adhesion-dependent functions, especially defective tissue emigration of neutrophils, leading to recurrent infection.

Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.

Cytokine-induced cell adhesion molecule present on activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. It is important for the recruitment of leukocytes to sites of inflammation. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, p154)

A subtype of tetraspanin proteins that play a role in cell adhesion, cell motility, and tumor metastasis. CD9 antigens take part in the process of platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg.

A family of polypeptides purified from snake venoms, which contain the arginine-glycine-aspartic acid (RGD) sequence. The RGD tripeptide binds to integrin receptors and thus competitively inhibits normal integrin-ligand interactions. Disintegrins thus block adhesive functions and act as platelet aggregation inhibitors.

Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.

Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.

Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

A cell-surface ligand involved in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

A cytoskeletal protein associated with cell-cell and cell-matrix interactions. The amino acid sequence of human vinculin has been determined. The protein consists of 1066 amino acid residues and its gene has been assigned to chromosome 10.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.

Specialized areas at the CELL MEMBRANE where a cell attaches to the EXTRACELLULAR MATRIX or other substratum.

Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).

White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).

A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers.

Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.

A genetically related subfamily of RAP GTP-BINDING PROTEINS that share homology with RAS PROTEINS. They bind to Ras effectors but do not activate them, therefore they may antagonize the effects of RAS PROTEINS. This enzyme was formerly listed as EC 3.6.1.47.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.

Transmembrane proteins consisting of a lectin-like domain, an epidermal growth factor-like domain, and a variable number of domains that are homologous to complement regulatory proteins. They are important cell adhesion molecules which help LEUKOCYTES attach to VASCULAR ENDOTHELIUM.

The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

Glycoproteins found on the membrane or surface of cells.

A purely physical condition which exists within any material because of strain or deformation by external forces or by non-uniform thermal expansion; expressed quantitatively in units of force per unit area.

Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.

Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.

Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.

Proteins prepared by recombinant DNA technology.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

Hexameric extracellular matrix glycoprotein transiently expressed in many developing organs and often re-expressed in tumors. It is present in the central and peripheral nervous systems as well as in smooth muscle and tendons. (From Kreis & Vale, Guidebook to the Extracellular Matrix and Adhesion Proteins, 1993, p93)

A cell line derived from cultured tumor cells.

A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.

An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.

The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.

Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

Antibodies that inhibit the reaction between ANTIGEN and other antibodies or sensitized T-LYMPHOCYTES (e.g., antibodies of the IMMUNOGLOBULIN G class that compete with IGE antibodies for antigen, thereby blocking an allergic response). Blocking antibodies that bind tumors and prevent destruction of tumor cells by CYTOTOXIC T-LYMPHOCYTES have also been called enhancing antibodies. (Rosen et al., Dictionary of Immunology, 1989)

Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.

The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type.

A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.

Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.

The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)

A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.

Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.

Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.

A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3.

A heterodimeric protein that is a cell surface antigen associated with lymphocyte activation. The initial characterization of this protein revealed one identifiable heavy chain (ANTIGENS, CD98 HEAVY CHAIN) and an indeterminate smaller light chain. It is now known that a variety of light chain subunits (ANTIGENS, CD98 LIGHT CHAINS) can dimerize with the heavy chain. Depending upon its light chain composition a diverse array of functions can be found for this protein. Functions include: type L amino acid transport, type y+L amino acid transport and regulation of cellular fusion.

Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.

Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.

A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.

Cell adhesion molecule and CD antigen that serves as a homing receptor for lymphocytes to lymph node high endothelial venules.

A fungal metabolite that blocks cytoplasmic cleavage by blocking formation of contractile microfilament structures resulting in multinucleated cell formation, reversible inhibition of cell movement, and the induction of cellular extrusion. Additional reported effects include the inhibition of actin polymerization, DNA synthesis, sperm motility, glucose transport, thyroid secretion, and growth hormone release.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

Restoration of integrity to traumatized tissue.

Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.

The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.

Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.

Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.

The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.

A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.

A RHO GTP-BINDING PROTEIN involved in regulating signal transduction pathways that control assembly of focal adhesions and actin stress fibers. This enzyme was formerly listed as EC 3.6.1.47.

Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.

A ubiquitously expressed syndecan that is found in all stages of embryonic development and in most adult tissues. Syndecan-4 is found localized to focal adhesion sites in fibronectin-adherent cells and may play a role the process of CELL MIGRATION and CELL PROLIFERATION.

A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.

The development of new BLOOD VESSELS during the restoration of BLOOD CIRCULATION during the healing process.

A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.

A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.

A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin.

A family of crosslinking filament proteins encoded by distinct FLN genes. Filamins are involved in cell adhesion, spreading, and migration, acting as scaffolds for over 90 binding partners including channels, receptors, intracellular signaling molecules and transcription factors. Due to the range of molecular interactions, mutations in FLN genes result in anomalies with moderate to lethal consequences.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.

A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.

An Ig superfamily transmembrane protein that localizes to junctional complexes that occur between ENDOTHELIAL CELLS and EPTHELIAL CELLS. The protein may play a role in cell-cell adhesion and is the primary site for the attachment of ADENOVIRUSES during infection.

Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.

Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.

Microscopy in which television cameras are used to brighten magnified images that are otherwise too dark to be seen with the naked eye. It is used frequently in TELEPATHOLOGY.

Methods for maintaining or growing CELLS in vitro.

Movement of tethered, spherical LEUKOCYTES along the endothelial surface of the microvasculature. The tethering and rolling involves interaction with SELECTINS and other adhesion molecules in both the ENDOTHELIUM and leukocyte. The rolling leukocyte then becomes activated by CHEMOKINES, flattens out, and firmly adheres to the endothelial surface in preparation for transmigration through the interendothelial cell junction. (From Abbas, Cellular and Molecular Immunology, 3rd ed)

The quantity of volume or surface area of CELLS.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.

A large family of MONOMERIC GTP-BINDING PROTEINS that are involved in regulation of actin organization, gene expression and cell cycle progression. This enzyme was formerly listed as EC 3.6.1.47.

The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.

A transmembrane glycoprotein subunit that can dimerize with a variety of light chain subunits (ANTIGENS, CD98 LIGHT CHAINS). This protein subunit serves a diverse array of functions including amino acid transport and cell fusion. Its function is altered depending which of the light chain subunits it interacts with.

Conjugated proteins in which mucopolysaccharides are combined with proteins. The mucopolysaccharide moiety is the predominant group with the protein making up only a small percentage of the total weight.

Venoms from SNAKES of the viperid family. They tend to be less toxic than elapid or hydrophid venoms and act mainly on the vascular system, interfering with coagulation and capillary membrane integrity and are highly cytotoxic. They contain large amounts of several enzymes, other factors, and some toxins.

Primary haemostasis: sticky fingers cement the relationship. (1/5403)

Platelet aggregation to form a haemostatic plug, or thrombus, plays a key role in preventing bleeding from a wound. Recent studies have provided new insights into how platelet receptors are deployed during the interactions with the vascular subendothelial matrix that lead to haemostatic plug formation. (+info)

The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells. (2/5403)

PINCH is a widely expressed and evolutionarily conserved protein comprising primarily five LIM domains, which are cysteine-rich consensus sequences implicated in mediating protein-protein interactions. We report here that PINCH is a binding protein for integrin-linked kinase (ILK), an intracellular serine/threonine protein kinase that plays important roles in the cell adhesion, growth factor, and Wnt signaling pathways. The interaction between ILK and PINCH has been consistently observed under a variety of experimental conditions. They have interacted in yeast two-hybrid assays, in solution, and in solid-phase-based binding assays. Furthermore, ILK, but not vinculin or focal adhesion kinase, has been coisolated with PINCH from mammalian cells by immunoaffinity chromatography, indicating that PINCH and ILK associate with each other in vivo. The PINCH-ILK interaction is mediated by the N-terminal-most LIM domain (LIM1, residues 1 to 70) of PINCH and multiple ankyrin (ANK) repeats located within the N-terminal domain (residues 1 to 163) of ILK. Additionally, biochemical studies indicate that ILK, through the interaction with PINCH, is capable of forming a ternary complex with Nck-2, an SH2/SH3-containing adapter protein implicated in growth factor receptor kinase and small GTPase signaling pathways. Finally, we have found that PINCH is concentrated in peripheral ruffles of cells spreading on fibronectin and have detected clusters of PINCH that are colocalized with the alpha5beta1 integrins. These results demonstrate a specific protein recognition mechanism utilizing a specific LIM domain and multiple ANK repeats and suggest that PINCH functions as an adapter protein connecting ILK and the integrins with components of growth factor receptor kinase and small GTPase signaling pathways. (+info)

Blocking very late antigen-4 integrin decreases leukocyte entry and fatty streak formation in mice fed an atherogenic diet. (3/5403)

Atherosclerotic lesion development is characterized by the recruitment of leukocytes, principally monocytes, to the vessel wall. Considerable interest has been focused on the adhesion molecule(s) involved in leukocyte/endothelial interactions. The goal of the present study was to determine the role of the very late antigen-4 (VLA-4) integrin/ligand interaction in fatty streak development using murine models. Because alpha4 null mice are not viable, a peptidomimetic was used to block VLA-4-mediated leukocyte binding. The ability of a synthetic peptidomimetic of connecting segment-1 (CS-1 peptide) to block the recruitment of leukocytes and the accumulation of lipid in the aortic sinus of either wild-type mice (strain C57BL/6J) or mice with a low-density lipoprotein null mutation (LDLR-/-) maintained on an atherogenic diet was assessed. The active (Ac) CS-1 peptide or scrambled (Sc) CS-1 peptide was delivered subcutaneously into mice using a mini osmotic pump. Mice were exposed to the peptide for 24 to 36 hours before the onset of the atherogenic diet. In C57BL/6J mice, leukocyte entry into the aortic sinus, as assessed by en face preparations, was inhibited by the active peptide (Ac=28+/-4, Sc=54+/-6 monocytes/valve; P=0.004). Additionally, frozen sections stained with Oil Red O were analyzed to assess lipid accumulation in the aortic sinus. C57BL/6J mice that received the (Ac) compound demonstrated significantly reduced lesion areas as compared with mice that received the (Sc) peptide (Ac=4887+/-4438 microm2, Sc=15 009 +/-5619 microm2; P<0.0001). In a separate study, LDLR-/- mice were implanted with pumps containing either the (Ac) or (Sc) peptide before initiation of the atherogenic diet. Because LDLR-/- mice fed a chow diet displayed small lesions at 14 weeks, the effects of the peptide seen in these animals represented a change in early lipid accumulation rather than initiation. By using whole-mount preparations, the (Ac) but not the (Sc) peptide significantly reduced the area of lipid accumulation in the aortic sinus, resulting in an approximate 66% decrease. Plasma analysis from all studies revealed concentrations of peptide to be present at levels previously determined by in vitro analysis to block adhesion. (Ac) CS-1 peptide, which blocks VLA-4 on the leukocyte surface, is effective in reducing leukocyte recruitment and lipid accumulation in the aortic sinus. The present study provides in vivo evidence that the VLA-4 integrin plays an important role in the initiation of the atherosclerotic lesion and lipid accumulation, and it suggests a potential therapeutic strategy for this disease. (+info)

Integrin subunit gene expression is regionally differentiated in adult brain. (4/5403)

Integrins are a diverse family of heterodimeric (alphabeta) adhesion receptors recently shown to be concentrated within synapses and involved in the consolidation of long-term potentiation. Whether neuronal types or anatomical systems in the adult rat brain are coded by integrin type was studied in the present experiments by mapping the relative densities of mRNAs for nine alpha and four beta subunits. Expression patterns were markedly different and in some regions complementary. General results and areas of notable labeling were as follows: alpha1-limited neuronal expression, neocortical layer V, hippocampal CA3; alpha3 and alpha5-diffuse neuronal and glial labeling, Purkinje cells, hippocampal stratum pyramidale, locus coeruleus (alpha3); alpha4- discrete limbic regions, olfactory cortical layer II, hippocampal CA2; alpha6-most prominently neuronal, neocortical subplate, endopiriform, subiculum; alpha7-discrete, all neocortical layers, hippocampal granule cells and CA3, cerebellar granule and Purkinje cells, all efferent cranial nerve nuclei; alpha8-discrete neuronal, deep cortex, hippocampal CA1, basolateral amygdala, striatum; alphaV-all cortical layers, striatum, Purkinje cells; beta4-dentate gyrus granule cells; beta5-broadly distributed, neocortex, medial amygdala, cerebellar granule and Purkinje cells, efferent cranial nerve nuclei; alpha2, beta2, and beta3-mRNAs not detected. These results establish that brain subfields express different balances of integrin subunits and thus different integrin receptors. Such variations will determine which matrix proteins are recognized by neurons and the types of intraneuronal signaling generated by matrix binding. They also could generate important differences in synaptic plasticity across brain systems. (+info)

The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. (5/5403)

Transforming growth factor beta (TGF beta) family members are secreted in inactive complexes with a latency-associated peptide (LAP), a protein derived from the N-terminal region of the TGF beta gene product. Extracellular activation of these complexes is a critical but incompletely understood step in regulation of TGF beta function in vivo. We show that TGF beta 1 LAP is a ligand for the integrin alpha v beta 6 and that alpha v beta 6-expressing cells induce spatially restricted activation of TGF beta 1. This finding explains why mice lacking this integrin develop exaggerated inflammation and, as we show, are protected from pulmonary fibrosis. These data identify a novel mechanism for locally regulating TGF beta 1 function in vivo by regulating expression of the alpha v beta 6 integrin. (+info)

Cell adhesion regulates the interaction between the docking protein p130(Cas) and the 14-3-3 proteins. (6/5403)

Integrin ligand binding induces a signaling complex formation via the direct association of the docking protein p130(Cas) (Cas) with diverse molecules. We report here that the 14-3-3zeta protein interacts with Cas in the yeast two-hybrid assay. We also found that the two proteins associate in mammalian cells and that this interaction takes place in a phosphoserine-dependent manner, because treatment of Cas with a serine phosphatase greatly reduced its ability to bind 14-3-3zeta. Furthermore, the Cas-14-3-3zeta interaction was found to be regulated by integrin-mediated cell adhesion. Thus, when cells are detached from the extracellular matrix, the binding of Cas to 14-3-3zeta is greatly diminished, whereas replating the cells onto fibronectin rapidly induces the association. Consistent with these results, we found that the subcellular localization of Cas and 14-3-3 is also regulated by integrin ligand binding and that the two proteins display a significant co-localization during cell attachment to the extracellular matrix. In conclusion, our results demonstrate that 14-3-3 proteins participate in integrin-activated signaling pathways through their interaction with Cas, which, in turn, may contribute to important biological responses regulated by cell adhesion to the extracellular matrix. (+info)

Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets. (7/5403)

Collagen-related peptide (CRP), a collagen homologue, induces platelet activation through a tyrosine kinase-dependent pathway, leading to sequential tyrosine phosphorylation of Fc receptor (FcR) gamma-chain, Syk, and phospholipase C-gamma2. Here we report that CRP and the platelet low affinity immune receptor FcgammaRIIA stimulate tyrosine phosphorylation of the T cell adapter SLP-76, whereas the G protein-coupled receptor agonist thrombin induces only minor tyrosine phosphorylation. This suggests that SLP-76 has a specific role downstream of receptors that signal via an immunoreceptor tyrosine-based activation motif. Immunoprecipitation studies demonstrate association of SLP-76 with SLAP-130, Vav, Fyn, Lyn, and the FcR gamma-chain in CRP-stimulated platelets. Several of these proteins, including SLP-76, undergo tyrosine phosphorylation in in vitro kinase assays performed on SLP-76 immunoprecipitates. Tyrosine phosphorylation of all of these proteins in the in vitro kinase assay was abrogated by the Src family kinase inhibitor PP1, suggesting that it is mediated by either Fyn or Lyn. The physiological significance of this is uncertain, however, since tyrosine phosphorylation of SLP-76 in vivo is not altered in either Fyn- or Lyn-deficient platelets. CRP stimulation of Syk-deficient platelets demonstrated that in vivo tyrosine phosphorylation of SLP-76 is downstream of Syk. The absence of Syk in the SLP-76 immunoprecipitates raises the possibility that another protein is responsible for bringing SLP-76 to Syk. Candidates for this include those proteins that co-immunoprecipitate with SLP-76, including the FcR gamma-chain. Tyrosine phosphorylation of PLC-gamma2 and Ca2+ mobilization is markedly attenuated in SLP-76-deficient platelets following CRP stimulation, suggesting that the adapter plays a critical role in the regulation of the phospholipase. The increase in tyrosine phosphorylation of SLAP-130 in response to CRP is also inhibited in SLP-76-deficient platelets, placing it downstream of SLP-76. This work identifies SLP-76 as an important adapter molecule that is regulated by Syk and lies upstream of SLAP-130 and PLC-gamma2 in CRP-stimulated platelets. (+info)

Expression pattern of integrin adhesion molecules in endometriosis and human endometrium. (8/5403)

Integrins are cell adhesion molecules that undergo cell-specific dynamic changes during the normal menstrual cycle in the human endometrium. Here, using immunohistochemistry, we have investigated the expression pattern of the integrins alphav, alpha2beta1, alpha3beta1, alpha3, alpha6, beta1, beta2 and beta3 in the human ectopic endometrium of 30 patients and in nine cases in the corresponding eutopic endometrium. The biopsies were obtained during the early or late follicular phase (25 cases), during the corpus luteum phase (four cases) and in one case after 6 months' treatment with a gonadotrophin releasing hormone (GnRH) agonist. The integrin expression was independent of the ovarian steroid situation at the time of biopsy. The integrin alpha6 was expressed in all endometriotic and endometrium samples. The integrin alpha3 was absent in all endometrium tissues of patients with endometriosis. However, the corresponding endometriotic lesions re-expressed this adhesion molecule in 15 cases. No change in integrin beta3 expression pattern could be demonstrated in either endometriotic lesions or endometrium samples, regardless of the menstrual cycle phase. A correlation between serum oestradiol and progesterone concentrations and the expression of the investigated integrins was not observed, thus indicating that these two hormones play a minor role in the regulation of the cell adhesion molecules examined. Our investigation suggests that endometriosis is a dedifferentiated disease as it expressed different integrins in comparison with the eutopic endometrium, and independently of the hormonal situation. The ability of endometriotic tissues to express integrins may explain the high recurrence rates in patients with endometriosis, as these samples retain their adhesion potency after retrograde menstruation and are thus able to establish cell-cell and cell-matrix interactions with the surrounding peritoneum. (+info)

Integrins are found in all animals while integrin-like receptors are found in plant cells. Integrins work alongside other ... The following are 16 of the ~24 integrins found in vertebrates: Beta-1 integrins interact with many alpha integrin chains. Gene ... integrins of the β2 family). This α-I domain is the binding site for ligands of such integrins. Those integrins that don't ... Which ligand in the ECM the integrin can bind to is defined by which α and β subunits the integrin is made of. Among the ...

https://en.wikipedia.org/wiki/Integrin

... (p150,95, CR4) is a complement receptor composed of CD11c and CD18. Integrin+alphaXbeta2 at the US ...

https://en.wikipedia.org/wiki/Integrin_alphaXbeta2

The CD49b protein is an integrin alpha subunit. It makes up half of the α2β1 integrin duplex. Integrins are heterodimeric ... Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell ... Integrin alpha-2, or CD49b (cluster of differentiation 49b), is a protein which in humans is encoded by the CD49b gene. ... "Entrez Gene: ITGA2 integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 receptor)". Gagliani, Nicola; Magnani, Chiara F.; Huber, ...

https://en.wikipedia.org/wiki/Integrin_alpha_2

... (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as ... and integrin αMβ2 thus belongs to the β2 subfamily (or leukocyte) integrins. αMβ2 is expressed on the surface of many ... Integrin+alphaM at the US National Library of Medicine Medical Subject Headings (MeSH) Mouse CD Antigen Chart Human CD Antigen ... Solovjov DA, Pluskota E, Plow EF (January 2005). "Distinct roles for the alpha and beta subunits in the functions of integrin ...

https://en.wikipedia.org/wiki/Integrin_alpha_M

This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen ... Integrin beta-1 is the most abundant beta-integrin expressed and associates with at least 10 different integrin-alpha subunits ... It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 ... The integrin beta-1B isoform appears to act as a dominant negative in that it inhibits cell adhesion. A second integrin beta-1 ...

https://en.wikipedia.org/wiki/Integrin_beta_1

Integrin alpha-6 is a protein that in humans is encoded by the ITGA6 gene. The ITGA6 protein product is the integrin alpha ... For example, alpha 6 may combine with beta 4 in the integrin referred to as TSP180, or with beta 1 in the integrin VLA-6. ... "Entrez Gene: ITGA6 integrin, alpha 6". De Arcangelis A, Hamade H, Alpy F, Normand S, Bruyère E, Lefebvre O, et al. (October ... Tani TT, Mercurio AM (September 2001). "PDZ interaction sites in integrin alpha subunits. T14853, TIP/GIPC binds to a type I ...

https://en.wikipedia.org/wiki/Integrin_alpha_6

Integrin alpha-5 is a protein that in humans is encoded by the ITGA5 gene. The product of this gene belongs to the integrin ... Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell ... Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes the ... "Entrez Gene: ITGA5 integrin, alpha 5 (fibronectin receptor, alpha polypeptide)". Tani, T T; Mercurio A M (Sep 2001). "PDZ ...

https://en.wikipedia.org/wiki/Integrin_alpha_5

Integrin beta-8 is a protein that in humans is encoded by the ITGB8 gene. This gene is a member of the integrin beta chain ... This protein noncovalently binds to an alpha subunit to form a heterodimeric integrin complex. In general, integrin complexes ... "Entrez Gene: ITGB8 integrin, beta 8". Reyes SB, Narayanan AS, Lee HS, Tchaicha JH, Aldape KD, Lang FF, Tolias KF, McCarty JH ( ... 2002). "The integrin αvβ8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-β1". J. Cell Biol. 157 (3 ...

https://en.wikipedia.org/wiki/Integrin_beta_8

True homologs of integrins exist in mammals, invertebrates, and some fungi but not in plant cells. Mammalian integrins are ... Integrin-like receptors (ILRs) are found in plants and carry unique functional properties similar to true integrin proteins. ... Integrin-like receptors and integrin-linked kinases together have been implicated in surface adhesion, immune response, and ion ... Most commonly, ILRs resembles the β1 subunit found in integrin proteins. This structural similarity between ILRs and integrins ...

https://en.wikipedia.org/wiki/Integrin-like_receptors

Integrin alpha-V is a protein that in humans is encoded by the ITGAV gene. ITGAV encodes integrin alpha chain V. Integrins are ... Porter JC, Hogg N (October 1998). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends ... many integrins are known to facilitate signal transduction. In mammals the integrins that include alpha-V are : Overexpression ... that combine with multiple integrin beta chains to form different integrins. Among the known associating beta chains (beta ...

https://en.wikipedia.org/wiki/Integrin_alpha_V

... is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as ... The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha ... "Thrombspondin acts via integrin-associated protein to activate the platelet integrin alphaIIbbeta3". J. Biol. Chem. 272 (23): ... Integrin beta-3 (β3) or CD61 is a protein that in humans is encoded by the ITGB3 gene. CD61 is a cluster of differentiation ...

https://en.wikipedia.org/wiki/Integrin_beta_3

... also CD49a is an integrin alpha subunit encoded in humans by the gene ITGA1. It makes up half of the α1β1 ... 1993). "Integrin and Arg-Gly-Asp dependence of cell adhesion to the native and unfolded triple helix of collagen type VI". Exp ... 1990). "Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but ... 1991). "Integrins in human cells and tumors". Cell Differ. Dev. 32 (3): 215-27. doi:10.1016/0922-3371(90)90034-T. PMID 2099238 ...

https://en.wikipedia.org/wiki/Integrin_alpha-1

Integrin alpha-10 also known as ITGA10 is a protein that in humans is encoded by the ITGA10 gene. Integrins are integral ... and sequence analysis of the integrin subunit alpha10, a beta1-associated collagen binding integrin expressed on chondrocytes ... Lehnert K, Ni J, Leung E, Gough S, Morris CM, Liu D, Wang SX, Langley R, Krissansen GW (1999). "The integrin alpha10 subunit: ... The I-domain containing alpha 10 combines with the integrin beta 1 chain (ITGB1) to form a novel collagen type II-binding ...

https://en.wikipedia.org/wiki/Integrin_alpha_10

CD11c is an integrin alpha X chain protein. Integrins are heterodimeric integral membrane proteins composed of an alpha chain ... "Entrez Gene: ITGAX integrin, alpha X (complement component 3 receptor 4 subunit)". Dyer KD, Garcia-Crespo KE, Killoran KE, ... Overview of all the structural information available in the PDB for UniProt: P20702 (Integrin alpha-X) at the PDBe-KB. This ... CD11c, also known as Integrin, alpha X (complement component 3 receptor 4 subunit) (ITGAX), is a gene that encodes for CD11c . ...

https://en.wikipedia.org/wiki/Integrin_alpha_X

The product of this gene belongs to the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane ... Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell ... "Entrez Gene: ITGA4 integrin, alpha 4 (antigen CD49D, alpha 4 subunit of VLA-4 receptor)". Hadari YR, Arbel-Goren R, Levy Y, ... Unlike other integrin alpha chains, alpha 4 neither contains an I-domain, nor undergoes disulfide-linked cleavage. Alpha 4 ...

https://en.wikipedia.org/wiki/Integrin_alpha_4

"Entrez Gene: ITGAD integrin, alpha D". Van der Vieren M, Le Trong H, Wood CL, et al. (1996). "A novel leukointegrin, alpha d ... 1999). "The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1". J. ... Integrin alpha-D is a protein that in humans is encoded by the ITGAD gene. GRCh38: Ensembl release 89: ENSG00000156886 - ... 1999). "alphadbeta2 integrin is expressed on human eosinophils and functions as an alternative ligand for vascular cell ...

https://en.wikipedia.org/wiki/Integrin_alpha_D

Integrin alpha-IIb is a protein that in humans is encoded by the ITGA2B gene. ITGA2B, also known as CD41, encodes integrin ... Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell ... Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. Alpha chain 2b undergoes ... "Entrez Gene: ITGA2B integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41)". Kato, Atsushi; Kawamata ...

https://en.wikipedia.org/wiki/Integrin_alpha_2b

Integrin alpha-3 is a protein that in humans is encoded by the ITGA3 gene. ITGA3 is an integrin alpha subunit. Together with ... ITGA3 encodes the integrin alpha 3 chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and ... "CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5". Mol. Hum. Reprod. 5 (2 ... "Entrez Gene: ITGA3 integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)". Park KR, Inoue T, Ueda M, Hirano T, ...

https://en.wikipedia.org/wiki/Integrin_alpha_3

"Entrez Gene: ITGA8 integrin, alpha 8". Schnapp LM, Hatch N, Ramos DM, et al. (1995). "The human integrin alpha 8 beta 1 ... 1998). "Utilization of a soluble integrin-alkaline phosphatase chimera to characterize integrin alpha 8 beta 1 receptor ... Integrin alpha-8 is a protein that in humans is encoded by the ITGA8 gene. GRCh38: Ensembl release 89: ENSG00000077943 - ... 2003). "Integrin alpha8beta1 mediates adhesion to LAP-TGFbeta1". J. Cell Sci. 115 (Pt 23): 4641-8. doi:10.1242/jcs.00145. PMID ...

https://en.wikipedia.org/wiki/Integrin_alpha_8

Integrin alpha-11 is a protein that, in humans, is encoded by the ITGA11 gene. This gene encodes an alpha integrin. Integrins ... integrin. A collagen-binding, I domain-containing, beta(1)-associated integrin alpha-chain present in muscle tissues". J. Biol ... 2006). "Integrin alpha 11 is a novel type I interferon stimulated gene". Cytokine. 33 (6): 352-61. doi:10.1016/j.cyto.2006.03. ... "Entrez Gene: ITGA11 integrin, alpha 11". Byström B, Carracedo S, Behndig AB, Gullberg D, Pedrosa-Domellof F (June 2009). "{ ...

https://en.wikipedia.org/wiki/Integrin_alpha_11

Integrin beta-6 is a protein that in humans is encoded by the ITGB6 gene. It is the β6 subunit of the integrin αvβ6. Integrins ... One α and one β subunit associate non-covalently to form 24 unique integrins found in mammals. While some β integrin subunits ... "Entrez Gene: ITGB6 integrin, beta 6". Hynes RO (September 2002). "Integrins: bidirectional, allosteric signaling machines". ... May 1996). "Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation ...

https://en.wikipedia.org/wiki/Integrin_beta_6

Alpha-7 integrin is a protein that in humans is encoded by the ITGA7 gene. Alpha-7 integrin is critical for modulating cell- ... Alpha-7 integrin is 128.9 kDa in molecular weight and 1181 amino acids in length. Integrins are heterodimeric integral membrane ... It was shown however that beta-1D integrin appears at embryonic day 11 and alpha-7 integrin does not appear until embryonic day ... The function of alpha-7 integrin, as is the case for most integrins is to mediate cell membrane interactions with extracellular ...

https://en.wikipedia.org/wiki/Integrin_alpha_7

... is an enzyme that in humans is encoded by the ILK gene involved with integrin-mediated signal ... Integrins lack enzymatic activity and depend on adapters to signal proteins. ILK is linked to beta-1 and beta-3 integrin ... Integrin-linked kinase (ILK), interacts with the cytoplasmic domain of beta-1 integrin. Multiple alternatively spliced ... Dedhar S, Williams B, Hannigan G (1999). "Integrin-linked kinase (ILK): a regulator of integrin and growth-factor signalling". ...

https://en.wikipedia.org/wiki/Integrin-linked_kinase

In molecular biology, CD18 (Integrin beta chain-2) is an integrin beta chain protein that is encoded by the ITGB2 gene in ... Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain, and are crucial for cells to be able ... The beta 2 integrins have also been found in a soluble form, meaning they are not anchored into the plasma membrane of the cell ... "ITGB2 integrin subunit beta 2 [ Homo sapiens (human) ]". Verma NK, Kelleher D (August 2017). "Not Just an Adhesion Molecule: ...

https://en.wikipedia.org/wiki/Integrin_beta_2

Integrin beta-7 is an integrin protein that in humans is encoded by the ITGB7 gene. It can pair with ITGA4 (CD49d) to form the ... Like all integrin subunits, β7 is a highly flexible, membrane-bound, extracellular protein that must pair with an α subunit for ... "Entrez Gene: ITGB7 integrin, beta 7". Byron A, Humphries JD, Askari JA, Craig SE, Mould AP, Humphries MJ (Nov 2009). "Anti- ... Yu Y, Zhu J, Mi LZ, Walz T, Sun H, Chen J, Springer TA (Jan 2012). "Structural specializations of α(4)β(7), an integrin that ...

https://en.wikipedia.org/wiki/Integrin_beta_7

Integrin, beta 4 (ITGB4) also known as CD104 (Cluster of Differentiation 104), is a human gene. Integrins are heterodimers ... Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This ... "Entrez Gene: ITGB4 integrin, beta 4". Aho S, Uitto J (Feb 1998). "Direct interaction between the intracellular domains of ... Suzuki S, Naitoh Y (Mar 1990). "Amino acid sequence of a novel integrin beta 4 subunit and primary expression of the mRNA in ...

https://en.wikipedia.org/wiki/Integrin_beta_4

Integrin beta-5 is a protein that in humans is encoded by the ITGB5 gene. Integrin, beta 5 has been shown to interact with PTK2 ... 1993). "A novel integrin specificity exemplified by binding of the alpha v beta 5 integrin to the basic domain of the HIV Tat ... ITGB5 encodes a subunit of integrin that can interact with several alpha chains to form a variety of integrin heterodimers. It ... Suzuki S, Huang ZS, Tanihara H (1990). "Cloning of an integrin beta subunit exhibiting high homology with integrin beta 3 ...

https://en.wikipedia.org/wiki/Integrin_beta_5

This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function- ... ITGAL gene encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha ... Porter JC, Hogg N (1999). "Integrins take partners: cross-talk between integrins and other membrane receptors". Trends Cell ... Integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide), also known as ITGAL, is ...

https://en.wikipedia.org/wiki/Integrin_alpha_L

Høye AM, Couchman JR, Wewer UM, Fukami K, Yoneda A (May 2012). "The newcomer in the integrin family: integrin α9 in biology and ... The α9 subunit forms a heterodimeric complex with a β1 subunit to form the α9β1 integrin. This integrin participates in cell ... Cytogenetic location: 3p22.2 This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins ... "Entrez Gene: ITGA9 integrin, alpha 9". Sulimova G, Kutsenko A, Rakhmanaliev E, Udina I, Kompaniytsev A, Protopopov A, Moisjak E ...

https://en.wikipedia.org/wiki/Integrin_alpha_9

... is a protein that in humans is encoded by the ITGBL1 gene. This gene encodes a beta integrin- ... "Entrez Gene: Integrin subunit beta like 1". Retrieved 2018-07-18. Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner ... The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants ...

https://en.wikipedia.org/wiki/Integrin_subunit_beta_like_1

Integrins are cell adhesion receptors that are evolutionary old and that play important roles during developmental and ... The β1 integrins, β2 integrins, and αv-containing integrins are the three largest groups in this kind of classification (Fig. 2 ... For integrins that require a tight control of activity, such as platelet integrin αIIβ3 and β2 integrins, precise activating ... Conformational changes in integrins. The crystallization of a soluble integrin heteodimer has made clear that integrins can ...

https://link.springer.com/article/10.1007/s00441-009-0834-6

... a molecule that mediates signaling through integrins, in a rare disorder characterized by spontaneous bleeding and ... Integrins, by switching from a resting low-affinity state to an active high-affinity conformation, can rapidly make blood cells ... A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans *Nikolay L Malinin ... Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation *Lena Svensson ...

https://www.nature.com/articles/nm0309-249?error=cookies_not_supported&code=222088c0-8b54-4d5e-bf22-8dc6e6314780

... Exp Cell Res. 1999 Apr 10;248(1):44-57. doi: 10.1006/excr. ...

https://pubmed.ncbi.nlm.nih.gov/10094812/?dopt=Abstract

Integrin_alpha; Integrin alpha cytoplasmic region. pfam08441. Location:617 → 958. Integrin_alpha2; Integrin alpha. ... Integrin_alpha; Integrin alpha cytoplasmic region. pfam08441. Location:616 → 957. Integrin_alpha2; Integrin alpha. ... Integrin_alpha; Integrin alpha cytoplasmic region. pfam08441. Location:628 → 933. Integrin_alpha2; Integrin alpha. ... Integrin_alpha; Integrin alpha cytoplasmic region. pfam08441. Location:628 → 969. Integrin_alpha2; Integrin alpha. ...

https://www.ncbi.nlm.nih.gov/gene/3681

AG Extracellular Matrix and Integrins in Cardiovascular Disease. Integrin signaling and heart failure Integrins are ... Integrin activation and atherosclerosis Although integrins are highly expressed on the cell surface, they do not bind their ... ß2 integrin activation on T cells is also a critical step during the process of extravasation and recruitment of T cells within ... Beta2-integrin activation on T cell subsets is an independent prognostic factor in unstable angina pectoris. Basic Res Cardiol ...

https://www.klinikum.uni-heidelberg.de/zentrum-fuer-innere-medizin-medizin-klinik/innere-medizin-iii-kardiologie-angiologie-und-pneumologie/forschung/forschung/grundlagenforschung/extracellular-matrix-and-integrins-in-cardiovascular-disease

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the recent global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the companys ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the companys patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions ...

https://www.merck.com/publication/discovery-of-a-new-class-of-integrin-antibodies-for-fibrosis/

Laskers go for integrins, prenatal testing, COVID-19 dashboard. Sep. 29, 2022 ... "for discoveries concerning the integrins, key mediators of cell-matrix and cell-cell adhesion in physiology and disease." ...

https://www.bioworld.com/articles/690115-laskers-go-for-integrins-prenatal-testing-covid-19-dashboard?v=preview

J:313791 Datta R, et al., Autoregulation of insulin receptor signaling through MFGE8 and the alphavbeta5 integrin. Proc Natl ...

http://www.informatics.jax.org/marker/MGI:96614

Integrin A (or I) domain. Timeline for Protein Integrin alpha2-beta1 from c.62.1.1: Integrin A (or I) domain: *Protein Integrin ... Protein Integrin alpha2-beta1 from c.62.1.1: Integrin A (or I) domain appears in SCOP 1.69. *Protein Integrin alpha2-beta1 from ... Protein Integrin alpha2-beta1 from c.62.1.1: Integrin A (or I) domain appears in the current release, SCOPe 2.08. ... Lineage for Protein: Integrin alpha2-beta1. *Root: SCOP 1.71 *. Class c: Alpha and beta proteins (a/b) [51349] (134 folds). ...

http://scop.berkeley.edu/sunid=53313&ver=1.71

Selected quality suppliers for anti-Integrin beta 3 antibodies. ... Order monoclonal and polyclonal Integrin beta 3 antibodies for ... Integrin beta 3 Antibodies. (Integrin beta 3 (ITGB3)). The ITGB3 protein product is the integrin beta chain beta 3. Integrins ... Find Integrin beta 3 Antibodies for a variety of species such as anti-Human Integrin beta 3, anti-Mouse Integrin beta 3, anti- ... integrin subunit beta 3 (Itgb3) Antibodies. integrin subunit beta 3 L homeolog (itgb3.L) Antibodies. integrin beta 3a (itgb3a) ...

https://www.antibodies-online.com/in/integrin-beta-3-48691/integrin-beta-3-antibodies-2606/

Content aggregated by Proteopedia from external resources falls under the respective resources copyrights. See the Terms of Service ...

https://proteopedia.org/wiki/index.php/Integrin_3D_structures

The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1.. 102. ... A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus.. ... A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus.. ... Online version: http://atlasgeneticsoncology.org/gene/41014/itgam-(integrin-subunit-alpha-m) ...

https://atlasgeneticsoncology.org/gene/41014/itgam-

... rabbit anti-β3 integrin and rabbit anti-β5 integrin (20 μg/ml; AB1932 and AB1926; Chemicon), mouse anti-β1 integrin (20 μg/ml; ... At 14 DIV, hippocampal neurons were immunolabeled with anti-β3 integrin antibody. Arrows point to examples of β3 integrin ... In addition to activating integrins, RGD-containing peptide may also interfere with endogenous ECM-integrin interactions at ... rabbit anti-β3 integrin and rabbit anti-β5 integrin (2 μg/ml; AB1932, AB1926; Chemicon), rabbit anti-NMDAR2A/B (1 μg/ml; AB1548 ...

https://www.jneurosci.org/content/26/6/1813

Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells. ... Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells. ... These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-β axis as a ... We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF- ...

https://www.jci.org/articles/view/142116/sd/1

Dual αV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic ... Dual αV-integrin and neuropilin-1 targeting peptide CEND-1 plus nab-paclitaxel and gemcitabine for the treatment of metastatic ... CEND-1 is a novel cyclic peptide that targets αV integrins and neuropilin-1 and enhances tumour delivery of co-administered ...

https://www.thelancet.com/pdfs/journals/langas/PIIS2468-1253

Among all the integrins, αvβ3 seems to be the most important in the process of tumor angiogenesis. Integrin αvβ3 is highly ... Integrin αvβ3 targeted radionuclide therapy. The crucial roles of integrin αvβ3 in tumor angiogenesis have led to a promising ... Although integrin αvβ3 has been extensively studied as one of the key players in tumor angiogenesis, other integrin members ... In addition, the high expression of integrin αvβ3 on tumor new-blood vessels and some tumor cells makes the integrin αvβ3 a ...

https://thno.org/v01p0201.htm

Re-imagining discovery and access to research: grants, datasets, publications, citations, clinical trials, patents and policy documents in one place.

https://app.dimensions.ai/details/patent/US-10059740-B2

The integrin β3 (ITGβ3) gene has been associated with both autism and the serotonin system. The purpose of this study was to ... The integrinβ3 (ITGβ3) gene has been associated with both autism and the serotonin system. The purpose of this study was to ... The integrinβ3 (ITGβ3) gene has been associated with both autism and the serotonin system. The purpose of this study was to ... The integrinβ3 (ITGβ3) gene is a subunit of the platelet- and megakaryocyte-specific heterodimeric fibrogen receptor and the ...

https://www.frontiersin.org/articles/10.3389/fpsyt.2012.00037/full

... integrin aIEL chain, and human mucosal lymphocyte antigen 1. It belongs to the integrin family and is primarily found on ... p,CD103 is a type I transmembrane glycoprotein also known as aE integrin, ... APC/Fire™ 750 anti-human CD103 (Integrin αE). Ber-ACT8. FC. PE/Fire™ 700 anti-human CD103 (Integrin αE) Antibody. Ber-ACT8. FC ... Brilliant Violet 711™ anti-human CD103 (Integrin αE). Ber-ACT8. FC. PE/Dazzle™ 594 anti-human CD103 (Integrin αE). Ber-ACT8. FC ...

https://www.biolegend.com/it-it/products/pedazzle-594-anti-human-cd103-integrin-alphae-antibody-14940

The truncated alphaIIb integrin protein is expressed by human leukemia, prostate adenocarcinoma, and melanoma cells but not by ... Integrin alphaIIb beta3 requires its cytoplasmic tails to participate in tumor cell adhesion, spreading, and migration. Using 3 ... To our knowledge, this is the first report of a naturally occurring variant of an alpha integrin that lacks the transmembrane ... Identification of a novel truncated alphaIIb integrin. ... Identification of a novel truncated alphaIIb integrin.. Cancer ...

https://go.drugbank.com/articles/A55795

Hence, integrins play a key role in various physiological as well as pathological processes, which has turned them into an ... Integrins are heterodimeric cell surface receptors, which enable adhesion, proliferation, and migration of cells by recognizing ...

https://www.cipsm.de/publications/research-area-c/integrin-modulators-a-patent-review/

Scalable synthesis of an integrin-binding peptide mimetic for biomedical applications. 23/11/2018 ...

https://thalesnano.com/post_publication/scalable-synthesis-of-an-integrin-binding-peptide-mimetic-for-biomedical-applications/

The role of beta1 integrin in modulating gut-homing alph. *Denucci, Christopher (PI) ... The role of beta1 integrin in modulating gut-homing alpha4beta7 on T cells ...

https://experts.umn.edu/en/projects/the-role-of-beta1-integrin-in-modulating-gut-homing-alph

... as one of the major proteins that was phosphorylated on tyrosine in response to β2 integrin activation. This β2 integrin- ... Ca2+ signalling mechanisms of the β2 integrin on neutrophils: involvement of phospholipase Cγ2 and Ins(1,4,5)P3 Carina HELLBERG ... 0.15 μM) inhibited both the β2 integrin-induced release of Ca2+ from intracellular stores and the subsequent influx of Ca2+ ... The relevance of these observations for the β2 integrin-induced Ca2+ signal was investigated using an inhibitor of PLC ...

https://portlandpress.com/biochemj/article-abstract/317/2/403/32147/Ca2-signalling-mechanisms-of-the-2-integrin-on?redirectedFrom=fulltext

Carbamylation of Integrin αIIbβ3: The Mechanistic Link to Platelet Dysfunction in ESKD. Veronika Binder, Barbara Chruścicka- ... Carbamylation of Integrin αIIbβ3: The Mechanistic Link to Platelet Dysfunction in ESKD ... Carbamylation of Integrin αIIbβ3: The Mechanistic Link to Platelet Dysfunction in ESKD ... Carbamylation of Integrin αIIbβ3: The Mechanistic Link to Platelet Dysfunction in ESKD ...

https://jasn.asnjournals.org/content/33/10/1841?with-ds=yes

The cyclic peptide, cRGDf[N(me)]V, binds to the alpha(v)beta(3) integrin and can disrupt binding of the integrin to its natural ... alpha(v)beta(3) integrins, ALPHA-V-BETA-3, ANGIOGENESIS, ANTAGONISTS, ANTITUMOR EFFICACY, CELLS, Endocytosis, EXPRESSION, IN- ... This information was compared to the binding and uptake properties of an alpha(v)beta(3) integrin-specific monoclonal antibody ... These results are discussed with regard to previous work indicating that RGD ligands enter cells by integrin-independent ...

http://www.chem.ubc.ca/binding-and-uptake-rgd-containing-ligands-cellular-alphavbeta3-integrins

β1 integrin-neutralizing antisera erased LTP when applied during, but not after, the return of integrin responsivity. Similarly ... Brefeldin A, which blocks integrin trafficking to the plasma membrane, prevented the delayed recovery of integrin responses to ... Neutralizing antisera selective for β1 integrins blocked these effects. TBS-induced integrin activation was brief (<7 min) ... activates β1 integrins, and integrin-signaling kinases, at spine synapses in adult hippocampal slices. ...

https://escholarship.org/uc/item/5hs5z3jp

Axon Medchem | Prime source supplier of high-value life science products, providing Axon Ligands™ for pharmaceutical research as world-wide recognized drug standards

https://www.axonmedchem.com/products/receptors/unclassified/integrin-receptors/sipa

1 integrin to its receptors, for example VCAM-1 (vascular cell adhesion molecule-1) and fibronectin; compounds that inhibit ... 1 integrin. In an especially preferred embodiment, &agr;4 &bgr;1 integrin is present on the surface of a white blood cell such ... 1 integrin to a protein comprising exposing the integrin to the protein in the presence of an effective inhibiting amount of a ... The integrin &agr;4&bgr;1 (also called VLA-4 for very late antigen-4) is a heterodimeric protein expressed on the surface of ...

https://patents.justia.com/patent/20030199692

Abstract 3454: Integrin-linked kinase and proximal signaling contributes to the cisplatin resistance of ovarian cancer cells. ...

https://aacrjournals.org/cancerres/crossref-citedby/595527

Integrins are cell adhesion receptors that are evolutionary old and that play important roles during developmental and pathological processes. (springer.com)
Integrins are cell adhesion receptors that are evolutionary old (Johnson et al. (springer.com)
When integrins were being identified with antibodies to integrin β subunits, several proteins were co-immunoprecipitated, and the number of subunits that composed the functional receptors was by no means obvious. (springer.com)
Integrins are heterodimeric surface receptors consisting of one α-chain and one ß-chain. (uni-heidelberg.de)
In a DFG funded project we are currently dissecting the role of integrin receptors in cardiac hypertrophy in vitro and in vivo by applying the conditional Tx-driven Cre-lox technology. (uni-heidelberg.de)
Integrins are heterodimeric cell surface receptors, which enable adhesion, proliferation, and migration of cells by recognizing binding motifs in extracellular matrix (ECM) proteins. (cipsm.de)
We report here that in rat and mouse, hippocampus cell adhesion receptors belonging to the β1-integrin family exhibit dynamic properties in adult synapses and that these contribute importantly to a previously unidentified stage of consolidation. (escholarship.org)
The integrin family consists of 18α- and 8β-glycoprotein subunits, forming at least 25 distinct heterodimeric receptors. (oncotarget.com)
Fibronectin (FN) matrix assembly is a multi-step process that involves binding to integrin receptors, FN-FN interactions and connections to the actin cytoskeleton. (princeton.edu)
Integrin-linked kinase (ILK) is a cytoplasmic effector of integrin receptors. (cdc.gov)
The integrins consist of at least three identified families: the cytoadhesin receptors (RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS . (bvsalud.org)
Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. (idrblab.net)
Eph receptors regulate cell migration and attachment to the extracellular matrix by modulating integrin activity. (genominfo.org)

One successful approach that was instrumental in the identification of integrins took advantage of antibodies that blocked cell adhesion (Horwitz et al. (springer.com)
Find Integrin beta 3 Antibodies for a variety of species such as anti-Human Integrin beta 3, anti-Mouse Integrin beta 3, anti-Rat Integrin beta 3. (antibodies-online.com)
Find Integrin beta 3 Antibodies validated for a specific application such as WB, FACS, IHC, ELISA. (antibodies-online.com)
Find Integrin beta 3 Antibodies with a specific Host. (antibodies-online.com)
Find available monoclonal or polyclonal Integrin beta 3 Antibodies. (antibodies-online.com)
Find Integrin beta 3 Antibodies with a specific conjugate such as FITC, Biotin, PE. (antibodies-online.com)
These effects were also accompanied by integrin-dependent actin reorganization and synapse remodeling, which were partially inhibited by function-blocking antibodies against β1 and β3 integrins. (jneurosci.org)
To date, numerous anti-angiogenic therapies based on integrin αvβ3 antagonism, including antibodies, peptides, small molecules, small interfering RNA (siRNA) have been investigated [ 12 ]. (thno.org)
The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs) were partially blocked by integrin alpha6beta1 antibodies (P (jefferson.edu)
f Overexpression and immunoprecipitation of integrin α2 (ITGA2) with MR14-E5, anti-His, or anti-ITGA2 antibodies. (biomedcentral.com)
g Overexpression and immunoprecipitation of integrin α3 (ITGA3) with ER7-A7, ET7-A8, anti-His, or anti-ITGA3 antibodies. (biomedcentral.com)
h Overexpression and immunoprecipitation of integrin αV (ITGAV) with MR1-B1, anti-FLAG, or anti-ITGAV antibodies. (biomedcentral.com)
Loss of response: Persistent signs and symptoms of active disease despite at least one induction and one maintenance regimen of the locally approved regimen of anti-TNF inhibitors, anti-integrins, anti-IL-12/23 monoclonal antibodies, JAK inhibitors, or S1Preceptor modulators. (who.int)

This gene belongs to the beta-2 integrin family of membrane glycoproteins, which are are composed of non-covalently linked alpha and beta subunits to form a heterodimer. (nih.gov)
Integrins consist of two genetically nonrelated subunits, α and β, which are noncovalently associated with each other. (thno.org)
The N-terminal globular VI domains of LMA5 and LMA1 can bind integrin subunits alpha3, alpha2, alpha4, alpha6 (not LMA1) and beta1 (Nielsen & Yamada 2001 - using mouse LMA1 and LMA5 against human integrins). (reactome.org)
The endo/exocytic trafficking of integrins is regulated by the small GTPase Rab21, which associates with several integrin α subunits. (vtt.fi)
Each family contains a common beta-subunit ( INTEGRIN BETA CHAINS ) combined with one or more distinct alpha-subunits ( INTEGRIN ALPHA CHAINS ). (bvsalud.org)

The integrin family is composed of 24 αβ heterodimeric members that mediate the attachment of cells to the extracellular matrix (ECM) but that also take part in specialized cell-cell interactions. (springer.com)
One reason for the difficulties encountered when trying to characterize the integrin family is that many of their ligands are large multi-adhesive extracellular matrix (ECM) molecules that, in addition to binding integrins, bind other proteins including ECM molecules, growth factors, cytokines, and matrix-degrading proteases. (springer.com)
Nur Ergebnisse in Extracellular Matrix and Integrins in Cardiovascular Disease anzeigen. (uni-heidelberg.de)
By establishing a Tamoxifen (Tx) inducible knockout mouse, we have demonstrated that the extracellular matrix glycoprotein fibronectin (Fn), activates critical survival signals via ß1 integrin following myocardial infarction (1). (uni-heidelberg.de)
Integrins represent a subclass of cell adhesion molecules connecting the cytoskeleton with the extracellular matrix (ECM) or other cells. (thno.org)
The cyclic peptide, cRGDf[N(me)]V, binds to the alpha(v)beta(3) integrin and can disrupt binding of the integrin to its natural ligands in the extracellular matrix. (ubc.ca)
Integrin αIIbβ3 can also bind other proteins on platelets and in blood as well as proteins within the intricate lattice that forms in the space between cells (extracellular matrix) to ensure proper clot formation and promote wound healing. (medlineplus.gov)

The gene is located about 11kb downstream of the integrin subunit alpha X gene, another member of the integrin family. (nih.gov)

Expression of the myeloid-specific leukocyte integrin gene CD11d during macrophage foam cell differentiation and exposure to lipoproteins. (nih.gov)
The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1. (atlasgeneticsoncology.org)
The leukocyte integrin α M β 2 (Mac-1) is a multiligand receptor that mediates a range of adhesive reactions of leukocytes during the inflammatory response. (elsevier.com)

Engagement of β 2 integrins triggers a tyrosine kinase-dependent intracellular mobilization and influx of Ca 2+ in human neutrophils. (portlandpress.com)
We recently reported that TGF-β1-stimulated collagen expression by cultured kidney cells requires integrin-dependent activation of focal adhesion kinase (FAK) and consequent ERK MAP kinase activity leading to Smad3 linker region phosphorylation. (northwestern.edu)
Among them, integrin-linked kinase 1 (ILK1) signaling pathway was first down-regulated but then up-regulated after treatment for prolonged period. (elsevier.com)
In these cells, the integrin α5 mediated focal adhesion kinase (FAK) signaling pathway was activated by AKR1B10, which, along with δ-catenin, stimulated Rac1-mediated cell migration and movement. (oncotarget.com)

In 1986, the antibody approach led to the expression cloning of cDNA encoding the chick integrin β1 subunit (Tamkun et al. (springer.com)
Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion. (nih.gov)
In this review, we summarize the current development and applications of antibody-, peptide-, and other ligand-based integrin targeted radiotherapeutics for tumor radiation therapy. (thno.org)
This information was compared to the binding and uptake properties of an alpha(v)beta(3) integrin-specific monoclonal antibody, LM609X. (ubc.ca)
Further, the collagen response was decreased by a function-blocking antibody or a peptide inhibitor of αvβ3-integrin. (northwestern.edu)
Natalizumab is a humanized IgG4 antibody directed at α4 subunit integrin, which blocks the α4β1 and α4β7 integrins, expressed on all leukocytes, with the exception of neutrophils, resulting active, but not selective for intestinal mucosa. (medscape.com)
Vedolizumab (MLN-02, LDP-02, MLN0002 or anti-α4β7) is a humanized antibody directed to α4β7 integrin that antagonizes binding to MAdCAM-1, but not to VCAM-1. (medscape.com)
Vedolizumab is a monoclonal antibody that selectively targets alpha4-beta7 integrin used for Crohn disease and hemorrhagic rectocolitis. (lww.com)

Integrin αvβ3 is highly expressed on activated endothelial cells, new-born vessels as well as some tumor cells, but is not present in resting endothelial cells and most normal organ systems, making it a suitable target for anti-tumor therapy. (thno.org)
In this work, the ability of a water-soluble, fluorescently labeled variant of the RGD-containing peptide (cRGDfK-488) to bind to integrins on human umbilical vascular endothelial cells (HUVEC) and subsequently undergo endocytosis was characterized. (ubc.ca)
Analysis of the expression of Pdgfrb during lymphatic development suggests that these defects probably arise from loss of α5β1 integrin in subsets of specialised Prox1(+)Pdgfrb(+) venous endothelial cells that are essential for the separation of the jugular lymph sac from the cardinal vein and formation of the lymphovenous valve leaflets. (uos.ac.uk)

The treatment of 14 d in vitro hippocampal neurons with arginine-glycine-aspartate (RGD)-containing peptide, an established integrin ligand, induced elongation of existing dendritic spines and promoted formation of new filopodia. (jneurosci.org)
CEND-1 is a novel cyclic peptide that targets αV integrins and neuropilin-1 and enhances tumour delivery of co-administered anticancer drugs. (thelancet.com)
The specificity of the RGD-containing peptide is assessed by comparison with control peptide that does not bind to the alpha(v)beta(3) integrin, cRADfK-488. (ubc.ca)
PN-943 is an orally delivered, gut-restricted alpha-4-beta-7 integrin specific antagonist peptide in development for the treatment of inflammatory bowel disease, with ulcerative colitis as the initial targeted indication. (pharmiweb.com)

The current review summarizes some basic facts about the integrin family including a historical perspective, their structure, and their ligand-binding properties. (springer.com)
Although integrins are highly expressed on the cell surface, they do not bind their respective ligand unless activated from within the cell (inside-out signaling). (uni-heidelberg.de)
This paradigm may have implications for mechanisms of promiscuity in ligand binding exhibited by integrin α M β 2 . (elsevier.com)
LM-511/521 has the highest affinity ligand for all LM-binding integrins except ofr alpha7 isoform X2beta1, while LM-411 has modest affinities for alpha6beta1 and alpha7 isoform X1beta1 (Nishiuchi et al. (reactome.org)

Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-β signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. (jci.org)
o2h Ventures has announced SEIS and EIS investment, alongside co-investment from the University of Nottingham's Invention Fund, into spin-out company Alevin Therapeutics to develop a platform of novel small molecule RGD integrin inhibitors with superior drug-like qualities. (o2hventures.com)
Originally the subject of a long-standing collaboration between academia and big pharma, scientists developed the platform of novel compounds with the aim of treating life-threatening conditions by limiting the activity of a key signaling pathway that is targeted by integrin inhibitors. (o2hventures.com)
Alevin is developing a proprietary platform of novel inhibitors of RGD integrins for the treatment of fibrosis, kidney disease and cancer. (o2hventures.com)
g.Patient must have inadequate response to, loss of response to, or intolerance of at least 1 of the following agents and no more than 2 classes of biologics: corticosteroids, immunosuppressant drugs, and/or TNF a antagonist therapy, anti-integrins, anti-IL-12/23, JAK inhibitors, and/or S1P receptor modulators. (who.int)

The integrinβ3 (ITGβ3) gene has been associated with both autism and the serotonin system. (frontiersin.org)
Here, we report that deletion of the gene encoding the integrin-α5 subunit (Itga5) using the Pdgfrb-Cre transgenic mouse line, leads to oedema, haemorrhage and increased levels of embryonic lethality. (uos.ac.uk)
The ITGA2B gene provides instructions for making one part, the alphaIIb subunit, of a receptor complex called integrin alphaIIb/beta3 (αIIbβ3), which is found on the surface of small cells called platelets. (medlineplus.gov)
The alphaIIb subunit attaches (binds) to the beta3 subunit, which is produced from the ITGB3 gene, to form integrin αIIbβ3. (medlineplus.gov)
The mutations that cause this disorder occur in both copies of the gene in each cell and impair the production or activity of the alphaIIb subunit, which disrupts the formation of functional integrin αIIbβ3. (medlineplus.gov)
Unlike Glanzmann thrombasthenia, this disorder results from a mutation in only one copy of the ITGA2B gene in each cell, and the mutations result in the formation of some integrin αIIbβ3 that is abnormally turned on (active), even when no clot is being formed. (medlineplus.gov)
Because the mutation that causes this disorder affects only one copy of the ITGA2B gene, some normal integrin is formed and normal platelets produced, which accounts for the mild signs and symptoms in affected individuals. (medlineplus.gov)
The role of ß3 integrin gene variants in Autism Spectrum Disorders--diagnosis and symptomatology. (cdc.gov)

Monocytes, lymphocytes, basophils and eosinophils are then able to firmly bind to VCAM-1 or fibronectin on the blood vessel wall via the &agr;4 &bgr;1 integrin. (justia.com)

This integrin binds the coagulation protein fibrinogea providing a key link between thrombosis and inflammation. (elsevier.com)
During clot formation, integrin αIIbβ3 binds to a protein called fibrinogen. (medlineplus.gov)
The overactive integrin αIIbβ3 binds inappropriately to clotting proteins within the cell during the formation of platelets, causing the platelets to become misshapen and large. (medlineplus.gov)
The fusion protein combines annexin V , which specifically recognizes and binds phosphatidylserine , with the disintegrin lebestatin (lbt), a polypeptide that specifically recognizes and binds integrin α1ß1. (bvsalud.org)
Also, it binds towards the somatomedin B area of vitronectin to avoid integrin-mediated binding towards the tripeptide Arg-Gly-Asp (RGD) area of vitronectin [3]. (exposed-skin-care.net)

The integrin &agr;4&bgr;1 (also called VLA-4 for very late antigen-4) is a heterodimeric protein expressed on the surface of monocytes, lymphocytes and two subclasses of granulocytes: cosinophils and basophils. (justia.com)

Taken together, the present data suggest that the β 2 integrin-induced Ca 2+ signal in human neutrophils is generated through activation of a PLCγ2-dependent pathway. (portlandpress.com)
Here, we defined a role for αvβ3-integrin in this non-canonical pathway. (northwestern.edu)
Treg-cell-specific deletion of integrin αvβ8 did not result in a spontaneous inflammatory phenotype, suggesting that this pathway is not important in Treg-cell-mediated maintenance of immune homeostasis. (lancs.ac.uk)
These data suggest that AKR1B10 promotes breast cancer metastasis through activation of the integrin α5 and δ-catenin mediated FAK/Src/Rac1 signaling pathway. (oncotarget.com)

CD103 is a type I transmembrane glycoprotein also known as aE integrin, integrin aIEL chain, and human mucosal lymphocyte antigen 1. (biolegend.com)

The main advance in the development of medications acting selectively on leukocyte recruitment has been on anti-integrins. (medscape.com)

WRAP-translation-exogenous-mRNA-based-induction-alpha-4-integrin-expression-human-mesenchymal-stem-cells-Boltze-2017.pdf - Published Version - Requires a PDF viewer. (warwick.ac.uk)

With this technique, we can demonstrate that ß2 integrin activation on T cells in patients with acute coronary syndrome (ACS), precedes future cardiovascular events and provides additional prognostic information over established biomarkers such as cardiac troponin (cTnT) or high-sensitive C-reactive protein (hsCRP) (6). (uni-heidelberg.de)
The ITGB3 protein product is the integrin beta chain beta 3. (antibodies-online.com)
The truncated alphaIIb integrin protein is expressed by human leukemia, prostate adenocarcinoma, and melanoma cells but not by platelets or normal prostate epithelial or normal breast epithelial cells. (drugbank.com)
Attachment of integrin αIIbβ3 from adjacent platelets to the same fibrinogen protein helps platelets cluster together (platelet cohesion) to form a blood clot. (medlineplus.gov)

ß2 integrin activation on T cells is also a critical step during the process of extravasation and recruitment of T cells within the atherosclerotic plaque. (uni-heidelberg.de)
We recently established a novel flow-cytometry based whole blood application to quantify functional ß2 integrin activation (induction of affinity and avidity) on T cell subpopulations. (uni-heidelberg.de)
Figure 2: Flow cytometric analysis of ß2 integrin activation of T cell subsets in whole blood. (uni-heidelberg.de)
We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-β activation. (jci.org)
Members of the integrin family play vital roles in the regulation of cellular activation, migration, proliferation, survival, and differentiation [ 8 , 9 ]. (thno.org)
In the present study we identified phospholipase Cγ2 (PLCγ2) as one of the major proteins that was phosphorylated on tyrosine in response to β 2 integrin activation. (portlandpress.com)
α4β1 also formed FNΔIII 1-7 multimers without the aid of exogenous stimulants, suggesting that an activated form of FN can override the need for activation of the integrin. (princeton.edu)

Integrins, a family of cell adhesion molecules, play key roles during tumor angiogenesis and metastasis. (thno.org)
Ectopic expression of AKR1B10 in breast cancer cells MCF-7 and MDA-MB-231 or siRNA-mediated silencing in BT-20 cells affected cell adhesion, migration and invasion in cell culture, and metastasis to the lung in the nude mice through upregulation of integrin α5 and δ-catenin. (oncotarget.com)

Integrins and dystroglycan indirectly connect the LM network to the actin cytoskeleton. (reactome.org)

1995 - mouse LM, rat alpha1 and beta1 integrins) and alpha-2 chains (Colognato et al. (reactome.org)

Identification of a novel truncated alphaIIb integrin. (drugbank.com)
Integrin alphaIIb beta3 requires its cytoplasmic tails to participate in tumor cell adhesion, spreading, and migration. (drugbank.com)

The 2022 Albert Lasker Basic Medical Research Award has been awarded to Richard Hynes, of the Massachusetts Institute of Technology, Erkki Ruoslahti, of the Sanford Burnham Prebys Medical Discovery Institute, and Timothy Springer, of Harvard Medical School "for discoveries concerning the integrins, key mediators of cell-matrix and cell-cell adhesion in physiology and disease. (bioworld.com)
Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. (antibodies-online.com)
Although αvβ3-integrin surface expression levels were not different, αvβ3-integrins colocalized with sites of focal adhesion significantly more in β1-k/d cells, and activated αvβ3-integrin was detected only in β1-k/d cells. (northwestern.edu)
Rab21 activity, integrin-Rab21 association, and integrin endocytosis are all necessary for normal cytokinesis, which becomes impaired when integrin-mediated adhesion at the cleavage furrow fails. (vtt.fi)
Adhesion molecules (e.g., selectins and integrins) are key modulators in mediating these cellular responses, such as leukocyte trafficking under shear stress. (gatech.edu)
Silencing of integrin α5 or δ-catenin eradicated the cell adhesion and migration enhanced by AKR1B10, both of which acted synergistically. (oncotarget.com)

Quantitative dual immunofluorescence microscopy showed that induction of long-term potentiation (LTP) by theta burst stimulation (TBS) activates β1 integrins, and integrin-signaling kinases, at spine synapses in adult hippocampal slices. (escholarship.org)

Integrin beta 3 is found along with the alpha IIb chain in platelets. (antibodies-online.com)
In this study, the authors found that platelets from patients with ESKD exhibit carbamylation-triggered structural alterations in integrin α IIb β 3 , associated with a fibrinogen-binding defect and impaired platelet aggregation. (asnjournals.org)

The relevance of these observations for the β 2 integrin-induced Ca 2+ signal was investigated using an inhibitor of PLC signalling pathways, 1-(6-{[17β-3-methoxyoestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1 H -pyrrole-2,5-dione (U73122). (portlandpress.com)
In the case of severe inflammation, treatment with purine analogue (azathioprine), TNF-alpha inhibitor (infliximab, adalimumab), or integrin inhibitor (vedolizumab) may be initiated. (lww.com)

It belongs to the integrin family and is primarily found on intestinal intraepithelial lymphocytes (IEL). (biolegend.com)

To our knowledge, this is the first report of a naturally occurring variant of an alpha integrin that lacks the transmembrane and cytoplasmic tail. (drugbank.com)

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice. (bvsalud.org)

Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. (antibodies-online.com)
Our experiments revealed that U73122 had no effect on either β 2 integrin-induced tyrosine phosphorylation of PLCγ2 (or any of the other proteins) or on the formation of Ins(1,4,5) P 3 , but it reduced the Ins(1,4,5) P 3 -induced release of 45 Ca 2+ from intracellular stores of electropermeabilized cells. (portlandpress.com)
A shortage (deficiency) of functional integrin αIIbβ3 prevents sufficient binding of fibrinogen or other proteins, impairing the formation of blood clots. (medlineplus.gov)

The interaction of HAb18G/CD147 with integrin alpha6beta1 and its impl" by Jing-yao Dai, Ke-feng Dou et al. (jefferson.edu)
The interaction of HAb18G/CD147 with integrin alpha6beta1 and its implications for the invasion potential of human hepatoma cells. (jefferson.edu)
The expression levels of HAb18G/CD147 and integrin alpha6beta1 were determined by immunofluorescent double-staining and confocal imaging analysis. (jefferson.edu)
Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin alpha6beta1. (jefferson.edu)
RESULTS: We found that integrin alpha6beta1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. (jefferson.edu)
The LM binding site for the major LM-binding integrins alpha6beta1, alpha6beta4, alpha3beta1 and alpha7beta1 (Belkin & Stepp 2000) is located in LG motifs 1-3 of LM alpha (LMA) chains (Hirosaki et al. (reactome.org)
2000 - mouse LMA4 with integrin alpha6beta1, Yu & Talts 2003 - mouse LMA5 with integrin alpha3beta1, Nishiuchi et al. (reactome.org)
Recombinant integrins vary in their laminin specificities: integrins alpha3beta1 and alpha6beta4 have a clear specificity for LM-332 and -511/512, integrin alpha6beta1 has a broad specificity, binding all LM isoforms with a preference for LM-111, -332 and -511/521. (reactome.org)

Finally, inhibition of αvβ3-integrin decreased Rac1 activity and COL1A2 promoter activity in β1-k/d cells. (northwestern.edu)
In conclusion, effective coupling of the integrin α1ß1-specific recognition molecule lbt confers stronger biological antimelanoma effects of ANV, which may be achieved by the dual effects of effective inhibition of B16F10 melanoma cell viability and inhibition of tumor tissue angiogenesis. (bvsalud.org)

Our findings show that integrins control ECM-mediated spine remodeling in hippocampal neurons through NMDAR/CaMKII-dependent actin reorganization. (jneurosci.org)
One of the hallmarks of integrin signaling is an increase in cell migration and invasion, both of which are associated with actin filament rearrangements. (cdc.gov)
Taken together, our results identify a mechanism through which ILK can regulate both integrin-associated rearrangements of actin filaments and cell migration and invasion at the integrin receptor-proximal region. (cdc.gov)

A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. (atlasgeneticsoncology.org)

Among all the integrins, αvβ3 seems to be the most important in the process of tumor angiogenesis. (thno.org)
Among all of the integrins, integrin αvβ3 has been identified as the most important member with overexpression pattern among vascular cells during tumor angiogenesis and vascular remodeling [ 1 , 10 , 11 ]. (thno.org)

The finding that β1 integrin neutralization was effective in the same time window for slice and behavioral experiments strongly suggests that integrin recovery triggers a temporally discrete, previously undetected second stage of consolidation for both LTP and memory. (escholarship.org)
A signaling complex that contains αvβ3 integrin detects bone and triggers this cytoskeletal reorganization. (rupress.org)

OPN through interaction with CD44 or several integrins is known to regulate multiple macrophage functions. (cdc.gov)
αv Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells. (hypermol.com)

2009. Matrix crosslinking forces tumor progression by enhancing integrin signaling. . (ucsf.edu)

Only a subset of integrins (8 out of 24) recognizes the RGD sequence in the native ligands. (springer.com)

Methods To investigate carbamylation as a potential mechanistic link between uremia and platelet dysfunction in ESKD, we used liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to quantify total homocitrulline, and biotin-conjugated phenylglyoxal labeling and Western blot to detect carbamylated integrin α IIb β 3 (a receptor required for platelet aggregation). (asnjournals.org)
It is estimated that 80,000 to 100,000 copies of integrin αIIbβ3 are present on the surface of each platelet. (medlineplus.gov)

These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-β axis as a potentially useful therapeutic target in GBM. (jci.org)
A human kidney tubular cell line in which β1-integrin was knocked down (β1-k/d) demonstrated enhanced type I collagen mRNA expression and promoter activity. (northwestern.edu)
Together, our results indicate that decreasing β1 chain causes αvβ3-integrin to become functionally dominant and promotes renal cell fibrogenesis via Rac1-mediated ERK activity. (northwestern.edu)
However, Treg cells lacking expression of integrin αvβ8 were unable to suppress pathogenic T cell responses during active inflammation. (lancs.ac.uk)
In conclusion, Rab21-regulated integrin trafficking is essential for normal cell division, and its defects may contribute to multinucleation and genomic instability, which are hallmarks of cancer. (vtt.fi)
Integrin-α5β1 is not required for mural cell functions during development of blood vessels but is required for lymphatic-blood vessel separation and lymphovenous valve formation. (uos.ac.uk)

This domain contains binding sites for alpha-dystroglycan, sulfated glycolipids, heparan sulfate chains and integrins. (reactome.org)

Previous studies indicated that a model in which two fibrinogen γC domain sequences, P1 (γ190-202) and P2 (γ377-395), serve as the α M β 2 binding sites cannot fully account for recognition of fibrinogen by integrin. (elsevier.com)

Vitronectin contains an RGD (45-47) sequence which is a binding site for membrane bound integrin s, e.g. the vitronectin receptor , which serve to anchor cells to the extra cellular matrix. (en-academic.com)

In these affinity protocols, the optimization of ion composition in the purification buffers was essential and resulted in the empirical finding that manganese ions (Mn 2+ ) increased integrin affinity (Gailit and Ruoslahti 1988 ). (springer.com)
Integrins, by switching from a resting low-affinity state to an active high-affinity conformation, can rapidly make blood cells sticky. (nature.com)

Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin alpha3beta1. (jefferson.edu)
However, it has never been investigated whether alpha3beta1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. (jefferson.edu)

CD11d β2 integrin expression on human NK, B, and γδ T cells. (nih.gov)

Although molecular mechanisms by which integrins affect synaptic efficacy have begun to emerge, their role in structural plasticity is poorly understood. (jneurosci.org)
Thus, there appear to be multiple, integrin-specific mechanisms for assembly of FN matrix. (princeton.edu)

Integrin α5β1 is essential for vascular development but it remains unclear precisely where and how it functions. (uos.ac.uk)

Brefeldin A, which blocks integrin trafficking to the plasma membrane, prevented the delayed recovery of integrin responses to TBS. (escholarship.org)
In cells lacking αvβ3- integrin, the responses were attenuated, whereas the response was enhanced in αvβ3-overexpressing cells. (northwestern.edu)

Anatomy28

Organisms4

Diseases1

Chemicals and Drugs100

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes30

Disciplines and Occupations1

Technology, Industry, Agriculture1

Information Science3

Primary haemostasis: sticky fingers cement the relationship. (1/5403)

The LIM-only protein PINCH directly interacts with integrin-linked kinase and is recruited to integrin-rich sites in spreading cells. (2/5403)

Blocking very late antigen-4 integrin decreases leukocyte entry and fatty streak formation in mice fed an atherogenic diet. (3/5403)

Integrin subunit gene expression is regionally differentiated in adult brain. (4/5403)

The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. (5/5403)

Cell adhesion regulates the interaction between the docking protein p130(Cas) and the 14-3-3 proteins. (6/5403)

Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets. (7/5403)

Expression pattern of integrin adhesion molecules in endometriosis and human endometrium. (8/5403)

Integrins

Antigens, CD29

Cell Adhesion

Integrin alphaV

Antigens, CD18

Integrin beta Chains

Receptors, Vitronectin

Integrin beta3

Integrin alpha4

Integrin alphaVbeta3

Fibronectins

Integrin alpha3beta1

Integrin alpha6beta1

Integrin alpha4beta1

Receptors, Fibronectin

Integrin alpha5beta1

Integrin alpha Chains

Integrin alpha5

Vitronectin

Cell Movement

Integrin alpha3

Laminin

Extracellular Matrix

Integrin alpha1beta1

Integrin alpha6

Talin

Oligopeptides

Cell Adhesion Molecules

Receptors, Collagen

Lymphocyte Function-Associated Antigen-1

Macrophage-1 Antigen

Integrin alpha2beta1

Antigens, CD

Signal Transduction

Cells, Cultured

Integrin alpha2

Antigens, CD11

Receptors, Lymphocyte Homing

Extracellular Matrix Proteins

Focal Adhesion Protein-Tyrosine Kinases

Antigens, CD151

Integrin alpha6beta4

Protein Binding

Antibodies, Monoclonal

Receptors, Cytoadhesin

Focal Adhesion Kinase 1

Focal Adhesions

Ligands

Antigens, CD11a

Integrin beta4

Receptors, Very Late Antigen

Cytoskeleton

Collagen

Receptors, Laminin

Cell Line

Paxillin

Amino Acid Sequence

Integrin alphaXbeta2

Molecular Sequence Data

Receptors, Leukocyte-Adhesion

CHO Cells

Platelet Glycoprotein GPIIb-IIIa Complex

Platelet Membrane Glycoproteins

Leukocyte-Adhesion Deficiency Syndrome

Neutrophils

Vascular Cell Adhesion Molecule-1

Antigens, CD9

Disintegrins

Endothelium, Vascular

Actins

Flow Cytometry

Cricetinae

Intercellular Adhesion Molecule-1

Protein Structure, Tertiary

Vinculin

Tumor Cells, Cultured

Protein-Tyrosine Kinases

Cell-Matrix Junctions

Antibodies

Leukocytes