1,721,030 research outputs found
Cleavage of urokinase receptor regulates its interaction with integrins in thyroid cells.
No full textThe urokinase-type plasminogen activator uPA-R can regulate integrin functions by associating with several types of beta-subunit. We have recently shown that normal thyroid TAD-2 cells express both a native and a cleaved form of uPA-R
which lacks the binding domain for uPA. We found this cleaved form to be present in reduced amounts in papillary and follicular thyroid carcinoma cells and completely absent in cells derived from an anaplastic thyroid carcinoma (ARO). We
now report that in normal thyroid cells the intact form of uPA-R strongly associates with beta-1 integrins, whereas its cleaved form does not. uPA-R expressed by ARO cells shows a stronger resistance to the cleavage mediated by uPA, plasmin and chymotrypsin than does uPA-R expressed by normal thyroid cells.
This resistance to cleavage correlates with the higher level of glycosylation of uPA-R of ARO cells as compared to that of cleavable uPA-R of normal thyroid cells. These results suggest that uPA-R cleavage, which occurs in several cell types, represents a mechanism regulating the interactions of uPA-R with integrins and, possibly, the subsequent integrin-mediated cell adhesion. Moreover we hypothesize that glycosylation regulates uPA-R cleavage and, indirectly, its interaction with integrins
The urokinase-receptor in infectious diseases.
No full textCell migration through the extracellular matrix (ECM) or endothelial cells is a basic process in several physiological and pathological events, including the immune host response to pathogens, both in the case of innate and adaptive immunity. The urokinase-type plasminogen activator (uPA) receptor (uPAR) is a GPI-anchored cell-surface receptor largely expressed on most of leukocytes, including monocytes/macrophages, granulocytes, immature dendritic cells. uPAR has been detected also in soluble and cleaved forms, which are increased in several pathologies. uPAR focuses the proteolytic activity of its ligand, the serine-protease uPA, on the cell membrane, thus promoting localized plasminogen activation and allowing the cell to degrade surrounding ECM and to move across physical barriers. However, the discovery that uPAR can bind with high affinity a component of the ECM, vitronectin (VN), and associates to cell surface molecules to activate signalling pathways inside the cells, largely expanded the role that uPAR can play in cell proliferation/survival and adhesion/migration, which are crucial events for an efficient immune response to infectious agents. This review is focused on the expression and possible functions of the various forms of uPAR in infectious diseases
Urokinase-type plasminogen-activator receptor associates to a cell surface molecule in monocytic cells.
No full textUrokinase-type plasminogen activator/type-2 plasminogen activator inhibitor complexes are not internalized upon binding to the urokinase-type plasminogen activator receptor in THP-1 cells
No full textThe urokinase receptor: A multifunctional receptor in cancer cell biology. therapeutic implications
No full textProteolysis is a key event in several biological processes; proteolysis must be tightly controlled because its improper activation leads to dramatic consequences. Deregulation of proteolytic activity characterizes many pathological conditions, including cancer. The plasminogen activation (PA) system plays a key role in cancer; it includes the serine-protease urokinase-type plasminogen activator (uPA). uPA binds to a specific cellular receptor (uPAR), which concentrates proteolytic activity at the cell surface, thus supporting cell migration. However, a large body of evidence clearly showed uPAR involvement in the biology of cancer cell independently of the proteolytic activity of its ligand. In this review we will first describe this multifunctional molecule and then we will discuss how uPAR can sustain most of cancer hallmarks, which represent the biological capabilities acquired during the multistep cancer development. Finally, we will illustrate the main data available in the literature on uPAR as a cancer biomarker and a molecular target in anti-cancer therapy
Multiple activities of a multifaceted receptor: roles of cleaved and soluble uPAR.
No full textThe urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell-surface receptor involved in many physiological and pathological events that include cell migration and tissue invasion. uPAR traditional role was considered the focusing of uPA proteolytic activity on the cell surface; however, different uPAR activities have been demonstrated in the last years. In fact, cell surface uPAR functionally interacts with integrins, fMLP-receptors (fMLP-Rs) and growth factor receptors, thus regulating cell adhesion, migration and proliferation. uPAR also exists in a soluble form (suPAR) that has been detected in human body fluids. Both cell surface and suPAR can be proteolytically cleaved, thus generating truncated forms lacking the N-terminal domain and exposing the specific sequence able to interact with the fMLP-Rs. The cleaved form of suPAR binds and activates the fMLP-Rs and regulates the activity of MCP-1, RANTES and SDF1 receptors. Here, we review the role that shedding and cleavage could play in regulating uPAR structural/functional interaction with other cell-surface receptors and in uPAR-mediated biological and pathological processes
Production of urokinase-type plasminogewn activator by normal and transformed rat thyroid cells in culture
No full textUrokinase-type plasminogen-activator up regulates the expression of its cellular receptor
No full textThe expression of the receptor for the urokinase-type plasminogen activator (uPAR) can be regulated by several hormones, cytokines, tumor promoters, etc. Recently, it has been reported that uPAR is capable of transducing signals, even though it is lacking a transmembrane domain and a cytoplasmatic tail. We now report that uPAR cell surface expression can be positively regulated by its ligand, uPA, in thyroid cells. The effect of uPA is independent of its proteolytic activity, since inactivated uPA or its aminoterminal fragment have the same effects of the active enzyme. The increase of uPAR on the cell surface correlates with an increase of specific uPAR mRNA. Finally, uPA up-regulates uPAR expression also in other cell lines of different type and origin, thus suggesting that the regulatory role of uPA on uPAR expression is not restricted to thyroid cells, but it occurs in different tissues, both normal and tumoral
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