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The same agent, however, can have opposite effects in different cell types.Many other cells in culture respond in the opposite manner when stimulated by these agents.In many of BURRIDGE ET AL these studies focal Eltrombopag adhesions have not been examined, but stress fibers disassemble and the cells develop a more arborized or stellate morphology.In a recent study, the catalytic subunit of this enzyme, which is active in the absence of the regulatory subunit, was microinjected into fibroblasts.This resulted in the dissolution of stress fibers, with a subsequent loss of focal adhesions. Several mitogenic growth factors also affect focal adhesions in receptive cells.For example, in the human epidermoid carcinoma line A, epi dermal growth factor stimulates increased membrane ruffling and disassembly of stress fibers as well as focal adhesions, as judged by staining for aactinin. Surprisingly, some focal adhesion staining with antitalin remained in response to PDGF, which suggests that the structures were not fully disassembled, but components such as vinculin were selectively released.A similar loss of vinculin from the focal adhesions of cultured smooth muscle cells has also been noted in response to PDGF. PDGF is a competence factor for these cells; other competence factors, such as fibro blast growth fa ctor, transforming growth factor p, and cholera toxin, also induced vinculin Cefuroxime sodium mobilization in these cells. The sequence of events leading to vinculin mobilization was investigated using a number of pharmacological reagents.It was concluded that activation of phospholipase C followed by elevated intracellular free calcium was important in mobilizing vinculin. The loss ofvinculin from focal adhesions was inhibited by specific protease inhibitors, which indicates that proteolysis, either ofvinculin or possibly some other protein, was involved.Some of these protease inhibitors are known to affect the type II isoform of the calciumdependent protease. Tumor promoters activate protein kinase C, the calcium activated, phospholipiddependent protein kinase that has been implicated in the mitogenic response of various growth factors, such as EGF and PDGF.The response of cultured cells to tumor promoters is often dra matic; the cells develop many of the characteristics of virally transformed cells.Epithelial cells often display the most pronounced response to tumor promoters, and the effect of these agents on the epithelial cytoskeleton has been investigated by several laboratories.The first signs of disruption, of stress fibers could be detected within min of TPA application; this was paralleled by extensive ruffling at the cell margins.The disruption of focal adhesions was confirmed both by IRM and by vinculin immunofluorescence. Accompanying its loss from focal ad hesions, vinculin could be detected within the membrane ruffles.Different cell types, as well as different agents, probably account for these apparently con flicting results.In this study it was shown that the ratio of filamentous to monomeric actin was unaffected by TPA even though the cells underwent a major reor ganization of their micro filament cytoskeleton.The effects ofTPA on BSC cells have also been studied in live cells microinjected with fluorescent, who noted that focal adhesions, as judged by IRM and vinculin distribution, persisted longer than stress fibers following TPA treatment.

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