Signal transduction

About: Signal transduction is a research topic. Over the lifetime, 122628 publications have been published within this topic receiving 8209258 citations. The topic is also known as: GO:0007165.

Signal transduction from the extracellular matrix.

Abstract: Adhesive interactions between cells and the insoluble meshwork of extracellular matrix proteins play a vital role in embryonic morphogenesis (33, 36, 94, 109, 135, 145), and in the regulation of gene expression in cells of the adult organism (1, 6, 105, 124). While the overall phenomenology ofextracellular matrix (ECM) 1 effects on cell differentiation is well known, the biochemical and molecular bases for these effects have remained elusive. It is clear that many of the interactions between cells and the ECM are mediated by the integrin family of cell surface receptors (2, 3, 13, 72). However, the precise mechanism(s) whereby signals from ECM proteins are transduced via integfins to the intraceUular machinery that controls cell growth, behavior, and differentiation, remains poorly defined. There are many compelling examples of control of cell differentiation and gene expression through adhesive interactions with extracellular matrix. In fibroblasts, cell attachment has been reported to rapidly increase expression of c-los and pro al(I) collagen messages (26, 27). Adhesion to fibronectin fragments, or cross-linking of the integfin oe5/~l fibronectin receptor with antibody, induced the expression of metalloprotease genes in fibroblastic cells; interestingly, intact fibronectin did not provoke this response nor did fibronectin fragments in solution (137). In a somewhat similar vein, stimulation of the C~v//~3 integrin in melanoma cells induced the expression of type IV collagenase and increased the invasive ability of these cells (115). The capacity of breast epithelial cells to express milk proteins in response to hormonal stimuli is quite dependent on the presence of an appropriate ECM (124). Studies in this system have led to the preliminary identification of matrix-dependent elements in the promoter region of the ~ casein gene (111). In the immune system, activation of T-lymphocytes through the T-cell antigen receptor is markedly enhanced by integrin-mediated adhesion to fibronectin or laminin (85, 97, 119). This process is part of a complex dialogue involving adhesive receptors occurring between mature T-cells and antigen presenting cells, as well as during lymphocyte differentiation (40, 132, 133). There is extensive signaling \"cross talk\" between

ER stress and the unfolded protein response.

Abstract: Conformational diseases are caused by mutations altering the folding pathway or final conformation of a protein. Many conformational diseases are caused by mutations in secretory proteins and reach from metabolic diseases, e.g. diabetes, to developmental and neurological diseases, e.g. Alzheimer's disease. Expression of mutant proteins disrupts protein folding in the endoplasmic reticulum (ER), causes ER stress, and activates a signaling network called the unfolded protein response (UPR). The UPR increases the biosynthetic capacity of the secretory pathway through upregulation of ER chaperone and foldase expression. In addition, the UPR decreases the biosynthetic burden of the secretory pathway by downregulating expression of genes encoding secreted proteins. Here we review our current understanding of how an unfolded protein signal is generated, sensed, transmitted across the ER membrane, and how downstream events in this stress response are regulated. We propose a model in which the activity of UPR signaling pathways reflects the biosynthetic activity of the ER. We summarize data that shows that this information is integrated into control of cellular events, which were previously not considered to be under control of ER signaling pathways, e.g. execution of differentiation and starvation programs.