ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1426759

出版商:Wiley    

年代:1992

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1426760

出版商:Wiley    

年代:1992

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1426761

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

The entry of glucose into muscle cells is achieved primarily via a carrier‐mediated system consisting of protein transport molecules. GLUT‐1 transporter isoform is normally found in the sarcolemmal (SL) membrane and is thought to be involved in glucose transport under basal conditions. With insulin stimulation, glucose transport is accelerated by translocating GLUT‐4 transporters from an intracellular pool out to the T‐tubule and SL membranes. Activation of transporters to increase the turnover number may also be involved, but the evidence is far from conclusive. When insulin binds to its receptor, it autophosphorylates tyrosine and serine residues on theβ‐subunit of the receptor. The tyrosine residues are thought to activate tyrosine kinases, which in turn phosphorylate/activate as yet unknown second messengers. Insulin receptor antibodies, however, have been reported to increase glucose transport without increasing kinase activity. Insulin resistance in skeletal muscle is a major characteristic of obesity and diabetes mellitus, especially NIDDM. A decrease in the number of insulin receptors and the ability of insulin to activate receptor tyrosine kinase has been documented in muscle from NIDDM patients. Most studies report no change in the intracellular pool of GLUT‐4 transporters available for translocation to the SL. Both the quality and quantity of food consumed can regulate insulin sensitivity. A high‐fat, refined sugar diet, similar to the typical U.S. diet, causes insulin resistance when compared with a low‐fat, complex‐carbohydrate diet. On the other hand, exercise increases insulin sensitivity. After an acute bout of exercise, glucose transport in muscle increases to the same level as with maximum insulin stimulation. Although the number of GLUT‐4 transporters in the sarcolemma increases with exercise, neither insulin or its receptor is involved. After an initial acute phase, which may involve calcium as the activator, a secondary phase of increased insulin sensitivity can last for up to a day after exercise. The mechanism responsible for the increased insulin sensitivity with exercise is unknown. Regular exercise training also increases insulin sensitivity, which can be documented several days after the final bout of exercise, and again the mechanism is unknown. An increase in the muscle content of GLUT‐4 transporters with training has recently been reported, Even though significant progress has been made in the past few years in understanding glucose transport in skeletal muscle, the mechanisms involved in regulating transport are far from being understood.— Barnard, R. J.; Youngren, J. F. Regulation of glucose transport in skeletal muscle.FASEB J.6: 3238‐3244; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1426762

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

A characteristic feature of the humoral immune response is a switch from IgM to other Ig iso‐types that typically occurs subsequent to a first exposure to antigen, intimately, isotype switching involves a DNA rearrangement that recombines a variable region gene, initially juxtaposed to theμconstant region gene (Cμ), with a constant region gene located downstream of Cμ.Isotype switching is controlled by T lymphocyte‐derived cytokines, such as interleukin‐4 (IL‐4), γ‐interferon (γ‐IFN), and TGFβ, which direct B lymphocytes to switch to specific Ig classes. For example, IL‐4, directs murine B cells to produce IgG1and IgE, and human B cells to produce IgE and IgG4. IL‐4 appears to direct switching to IgE and IgG1by inducing transcription of the ∊ and γ1 constant region genes before switch recombination. However, IL‐4 is not a sufficient stimulus for isotype switching, and additional signals are required to complete this process. This second signal can be provided by physical contact with activated T cells, which may involve, at least in part, ligation of the CD40 molecule. For murine B cells the second signal may also be provided by IL‐5. Isotype switching in B lymphocytes may provide a useful model for directed DNA recombination in higher eukaryotes.— Purkerson, J.; Isakson, P. A two‐signal model for regulation of immunoglobin isotype switching.FASEB J.6: 3245‐3252; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1385241

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Transferrin (Tf) is the iron‐transport protein of vertebrate serum. It is essentially synthesized in the liver, but lower amounts are also produced in other organs, such as testis and brain. A number of studies have been done to characterize the transcriptional elements implicated in the regulation of Tf gene expression in different organs. The results of these studies support the hypothesis that the Tf gene makes use of different combinations of nuclear proteins in different subsets of cells to achieve tissue‐specific expression. It is interesting to point out that this occurs in tissues arising from different embryological origin.— Zakin, M. M. Regulation of transferrin gene expression.FASEB J.6: 3253‐3258; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1426763

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Trypanosoma cruzi, the parasitic protozoan that causes the American trypanosomiasis, or Chagas disease, contains a number of antigenic molecules, some of which have tandems of amino acid repeats. One of these molecules, SAPA (shed acute phase antigen), contains a so‐far uniquetrans‐sialidase activity that is essential for penetration of the parasite into mammalian cells. The enzyme consists of two different domains, one presumably enzymatic, which contains four copies of an amino acid motif conserved in bacterial neuraminidases, and the other highly antigenic, consisting of the repeats. Another enzyme that seems to be involved in the host‐parasite relationship, the cysteine proteinase cruzipain, is also made up in its mature form of a catalytic domain with high homology to cathepsin L and a COOH‐terminal domain that is highly antigenic in vivo. These bifunctional molecules may have arisen by incorporation of a highly antigenic domain to an essential enzyme in order to attract the immune response, thus protecting the enzyme activity.— Cazzulo, J. J.; Frasch, A. C. C. SAPA/trans‐sialidase and cruzipain: two antigens fromTrypanosoma cruzicontain immunodominant but enzymatically inactive domains.FASEB J.6: 3259‐3264; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1426764

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

This manuscript describes the design of new vaccines based on synthetic peptides. To this end, we first analyze the structural basis of antigenic reactivity and specificity and the various types of epitopes that form the mosaics of macromolecular antigens, as well as the regulatory mechanisms involved in immune recognition. A distinction is made between sequential or continuous epitopes, and discontinuous or conformational ones, which are the majority of epitopes in globular proteins. In this context it is of particular interest to identify epitopes reacting with B cells and T cells, respectively, or with cytotoxic T cells, in association with the major histocompatibility cell‐surface antigens, and the role of these interactions in protective immunity. Identification of such epitopes in proteins of viral, bacterial, or parasitic organisms led to the synthesis of peptides, which when used in conjunction with appropriate carriers and/or adjuvants induced neutralizing antibodies. Particular examples are described, including: bacterial epitopes and mainly those of toxins of diphtheria, cholera, and shigella, leading not only to neutralizing antibodies but also to protective immunity against the deleterious effects of the respective toxins; parasite epitopes, such as those leading to anti‐malaria vaccine, based on either the sporozoite or the merozoite stage antigens; viral epitopes leading to protective immunity, with special emphasis on influenza virus where induction of CTL is crucial; and finally, synthetic peptide vaccines against HIV, which should lead to broad specificity protective immunity while avoiding the risks of a vaccine based on the infectious agent. The rapid recent progress in this field, as described in this review, increases the prospect of constructing successful synthetic peptide vaccines in the not too distant future.— Arnon, R.; Van Regenmortel, M. H. V. Structural basis of antigenic specificity and design of new vaccines.FASEB J.6: 3265‐3274; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1385242

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Protein tyrosine kinases (PTKs) are members of a growing family of oncoproteins and protooncoproteins that play a pivotal role in normal and abnormal proliferative processes. This hallmark identifies these unique proteins as potential targets for antiproliferative therapy. This review discusses the current status of PTK inhibitors, with special emphasis on tyrphostins as antiproliferative agents and as potential drugs for cancers, leukemias, psoriasis, and restenosis as well as other proliferative conditions. The development of tyrphostins as selective signal blockers can be viewed as a first step toward the development of “smart” cocktails as antiproliferative agents. Each of these custom‐made cocktails will be aimed at proliferative conditions whose transduction pathways can be characterized by molecular tools. The review also discusses the use of PTK blockers as tools to study signal transduction processes in which protein tyrosine kinases are implicated.— Levitzki, A. Tyrphostines: tyrosine kinase blockers as novel antiproliferative agents and dissectors of signal transductionFASEB J.6: 3275‐3282; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1426765

出版商:Wiley    

年代:1992

数据来源: WILEY

摘要:

Among the intracellular milieu of proteins are molecules with defined biochemical functions that serve as substrates for ligand‐activated tyrosine kinase receptors. It seems likely that some of these substrate molecules are elements of a critical signaling pathway used by growth factors to control cell proliferation and subverted by oncogenes to deregulate this process. Although the process of cell growth and division is relatively slow compared with other hormonally regulated responses, homeostasis in a human being requires approximately 20 × 106cell divisions per second for the renewal of various cell populations. This review summarizes the present understanding of tyrosine kinase substrates that seem likely to have key roles in the signal transduction pathway that regulates cell proliferation. This includes structural features of these molecules, the influence of tyrosine phosphorylation on their functions, the biological roles of these proteins, and the capacity of these substrates to associate with activated receptor tyrosine kinases.— Carpenter, G. Receptor tyrosine kinase substrates: src homology domains and signal transduction.FASEB J.6: 3283‐3289; 1992.

ISSN:0892-6638    

DOI:10.1096/fasebj.6.14.1385243

出版商:Wiley    

年代:1992

数据来源: WILEY