Integrins: a family of cell surface receptors.
TL;DR: This brief review of sequence data from embryogenesis, thrombosis, and lymphocyte help and killing is summarized and attempts to clarify the relationships among the members of this family of cell surface receptors.
About: This article is published in Cell.The article was published on 1987-02-27. It has received 4229 citations till now. The article focuses on the topics: Integrin & Cell adhesion.
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10,063 citations
TL;DR: Current structural and cell biological data suggest models for how integrins transmit signals between their extracellular ligand binding adhesion sites and their cytoplasmic domains, which link to the cytoskeleton and to signal transduction pathways.
8,275 citations
Cites background from "Integrins: a family of cell surface..."
...Figure 1 shows the complete mammathe recognition of the integrin receptor family around lian set (based on extensive searches of the human and 15 years ago (Hynes, 1987), they have become the best- mouse genomic sequences, C.A. Whittaker and R.O.H., understood cell adhesion receptors....
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...Figure 1 shows the complete mammathe recognition of the integrin receptor family around lian set (based on extensive searches of the human and 15 years ago (Hynes, 1987), they have become the best- mouse genomic sequences, C....
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TL;DR: Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses.
Abstract: The adhesive interactions of cells with other cells and with the extracellular matrix are crucial to all developmental processes, but have a central role in the functions of the immune system throughout life Three families of cell-surface molecules regulate the migration of lymphocytes and the interactions of activated cells during immune responses
6,595 citations
TL;DR: Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
Abstract: Rapid progress has been made in the understanding of the molecular interactions that result in cell adhesion. Many adhesive proteins present in extracellular matrices and in the blood contain the tripeptide arginine-glycine-aspartic acid (RGD) as their cell recognition site. These proteins include fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor. The RGD sequences of each of the adhesive proteins are recognized by at least one member of a family of structurally related receptors, integrins, which are heterodimeric proteins with two membrane-spanning subunits. Some of these receptors bind to the RGD sequence of a single adhesion protein only, whereas others recognize groups of them. The conformation of the RGD sequence in the individual proteins may be critical to this recognition specificity. On the cytoplasmic side of the plasma membrane, the receptors connect the extracellular matrix to the cytoskeleton. More than ten proved or suspected RGD-containing adhesion-promoting proteins have already been identified, and the integrin family includes at least as many receptors recognizing these proteins. Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.
4,821 citations
TL;DR: General themes are emerging that yield new strategies for prognosis and therapy of hu- man metastatic cancer, and an imbalanced regulation of motility and proteoly- sis appears to be required for invasion and metastasis.
2,776 citations
Cites background from "Integrins: a family of cell surface..."
...The first step is binding of the tumor cell to the basement membrane surface mediated by tumor cell surface receptors of the integrin (Hynes, 1987; Humphries et al., 1988) and nonintegrin (Rao et al....
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References
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TL;DR: The RGD sequence as a basic unit of a widespread cellular recognition system is established and the same peptides also inhibit the attachment of fibroblasts to a number of other proteins, including vitronectin.
1,363 citations
TL;DR: The interaction of the purified CSAT antigen with these cytoskeletal components is investigated, and an interaction specifically between theCSAT antigen and talin is demonstrated.
Abstract: Many observations suggest the presence of transmembrane linkages between the cytoskeleton and the extracellular matrix. In fibroblasts both light and electron microscopic observations reveal a co-alignment between actin filaments at the cell surface and extracellular fibronectin1–3. These associations are seen at sites of cell matrix interaction, frequently along stress fibres and sometimes where these bundles of microfilaments terminate at adhesion plaques (focal contacts). Non-morphological evidence also indicates a functional linkage between the cytoskeleton and extracellular matrix. Addition of fibronectin to transformed cells induces flattening of the cells and a reorganization of the actin cytoskeleton, with the concomitant appearance of arrays of stress fibres4–6. Conversely, disruption of the actin cytoskeleton by treatment with cytochalasin B leads to release of fibronectin from the cell surface7. As yet, there is no detailed knowledge of the molecules involved in this transmembrane linkage, although several proteins have been suggested as candidates in the chain of attachment between bundles of actin filaments and the cytoplasmic face of the plasma membrane: these include vinculin8, α-actinin9 and talin10, each one having been identified at regions where bundles of actin filaments interact with the plasma membrane and underlying cell-surface fibronectin10–13. Recently, the cell-substrate attachment (CSAT) antigen14 has been identified as a plasma membrane receptor for fibronectin15, raising the possibility that this glycoprotein complex may serve as a bridge between fibronectin and one or more of the underlying cytoskeletal components mentioned. Here we have investigated the interaction of the purified CSAT antigen with these cytoskeletal components, and we demonstrate an interaction specifically between the CSAT antigen and talin.
1,190 citations
TL;DR: Recognition of the molecular pathogenesis of this disorder has allowed rich insights into the role of cellular adherence reactions in inflammation and host defense.
Abstract: Leukocyte adhesion deficiency (LAD) is a recently recognized autosomal-recessive trait characterized by recurrent bacterial infections, impaired pus formation and wound healing, and abnormalities in a wide spectrum of adherence-dependent functions of granulocytes, monocytes, and lymphoid cells. Features of this disease are attributable to deficiency (or absence) of cell surface expression of a family of functionally and structurally related glycoproteins. These include Mac-1 (complement receptor type 3), lymphocyte function-associated antigen-1 (LFA-1), and p150,95. Defective biosynthesis of the beta chain shared by each molecule (comprised of alpha 1 beta 1 complexes) represents the fundamental molecular basis of this disease. Recognition of the molecular pathogenesis of this disorder has allowed rich insights into the role of cellular adherence reactions in inflammation and host defense.
1,096 citations
TL;DR: Affinity chromatography on wheat germ agglutinin-Sepharose showed that the 140 kd protein is a glycoprotein and, in combination with the fibronectin fragment chromatography, gave highly enriched preparations of the 140Kd protein.
1,094 citations
TL;DR: The results establish the existence of a family of adhesion receptors that recognize the sequence Arg-Gly-Asp, which corresponds to the cell adhesion site in fibronectin and is also present in the alpha chain of fibrinogen.
Abstract: Adhesive interactions of the platelet surface with plasma proteins such as fibrinogen and fibronectin play an important role in thrombosis and hemostasis. The binding of both of these proteins to platelets is inhibited by synthetic peptides containing the sequence Arg-Gly-Asp, which corresponds to the cell adhesion site in fibronectin and is also present in the alpha chain of fibrinogen. An affinity matrix made of an insolubilized heptapeptide containing the Arg-Gly-Asp sequence selectively binds the platelet membrane glycoprotein IIb/IIIa from detergent extracts of platelets. When incorporated into liposome membranes, the isolated protein confers to the liposomes the ability to bind to surfaces coated with fibrinogen, fibronectin, and vitronectin but not to surfaces coated with thrombospondin or albumin. This platelet receptor is related to the previously identified fibronectin and vitronectin receptors in that it recognizes an Arg-Gly-Asp sequence but differs from the other receptors in its wider specificity toward various adhesive proteins. These results establish the existence of a family of adhesion receptors that recognize the sequence Arg-Gly-Asp.
915 citations