Protein secretion, functional proteins

Semaphorins are secreted, membrane-associated or transmembrane proteins defined by the presence of a sema-phorin protein domain (Serna domain). In the mammalian system, more than 20 semaphorins have been identified which play important roles in a variety of tissues. The best characterized receptors for mediating semaphoiin effects are members of the neuropilin and plexin families of transmembrane proteins. Semaphoiin functions are best described in the regulation of neural development, angiogenesis, immunoregulation and cancer. 

It is now recognised that the function of the immune system is carefully regulated by cytokines, small (8.5-40 kDa) proteins secreted by immune cells and by tissue cells such as endothelial cells and fibroblasts. T helper cells and macrophages are major sources of cytokines during inflammatory... 

Young, G. M., Schmiel, D. H., and Miller, V. L. (1999). A new pathway for the secretion of virulence factors by bacteria the flagellar export apparatus functions as a protein-secretion system. Proc. Natl. Acad. Sci. U.S.A. 96, 6456-6461. 

A major goal in recombinant DNA technology is the production of useful foreign proteins by bacteria, yeast, or other cultured cells. Protein synthesis depends upon both transcription and translation of the cloned genes and may also involve secretion of proteins from the host cells. The first step, transcription, is controlled to a major extent by the structures of promoters and other control elements in the DNA (Chapter 28). Since eukaryotic promoters often function poorly in bacteria, it is customary to put the cloned gene under the control of a strong bacterial or viral X promoter. The latter include the X promoter PL (Fig. 28-8) and the lac (Fig. 28-2) and trp promoters of E. coli. These are all available in cloning vehicles. 

Many proteins synthesized in a cell are modified. For example, carbohydrates are often attached to the proteins found in cell membrane. Some proteins become phosphorylated. Such modifications either activate or inactivate the function of the protein. Therefore, a foreign gene should be properly manipulated to obtain a correct post-translational modification. For example, if an attachment of a carbohydrate to a protein is desired, one may design the process so as to secrete the protein out of a cell membrane. During this procedure the protein can be properly modified. However, such modification mechanisms can be different in each living organism. Therefore, careful selection of a proper cell line is necessary. 

The interferons are a family of proteins secreted by animal cells in response to viral and parasitic infections, and are part of the host s defence mechanism. They display multiple activities, affecting the functioning of the immune system, cell proliferation, and cell differentiation, primarily by inducing the synthesis of other proteins. Accordingly, they have potential as antiviral, antiprotozoal, immunomodulatory, and cell growth regulatory agents. 

The anterior surface of the eye is constantly rinsed by tear fluid secreted at a flow rate of about 1 pL/min by the main lachrymal gland of the lachrymal apparatus. Tears eventually drain into the nasal cavity through the nasolachrymal ducts. Tear fluid contains mucin, lysozyme, lactoferrin, prealbumin, and serum proteins. It functions as an antibacterial lubricant and aids in draining out foreign substances. The normal volume of tear fluid is 5 to 10 xL.66... 

The aquaporins are a family of small, integral membrane proteins that function as plasma membrane transporters of water and in some cases small polar solutes. There are at least 10 distinct aquaporins in mammals with specific expression patterns in epithelial, endothelial, and other tissues. Studies in aquaporin-null mice indicated a key role for aquaporins in the urinary concentrating mechanism, fluid secretion of glands, brain swelling, skin moisture, hearing and vision, and gastrointestinal absorption.62... 

Fig. 1. A model for the pleiotropic effects of LH on functions of Leydig cells. LH interacts with its specific receptor in the plasma membrane of the Leydig cell which results in the activation of several transducing systems and the formation of several second messengers (cyclic AMP, Ca2+, diacylglycerol and arachidonic acid metabolites). Protein kinases (A, C and calmodulin dependent) are activated resulting in the phosphorylation of specific proteins and the synthesis of specific proteins. The (phospho)proteins are involved in the transport of cholesterol to, and the control of, cholesterol metabolism in the inner mitochondrial membrane. Arachidonic acid metabolites (prostaglandins, leukotrienes) may also control steroidogenesis. LH can also regulate the secretion of proteins. The trophic effects of LH are manifested in the growth and differentiation of the Leydig cells.

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