ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2753268

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Hormones, neurotransmitters, and autacoids interact with specific receptors and thereby trigger a series of molecular events that ultimately produce their biological effects. These receptors, localized in the plasma membrane, carry binding sites for ligands as diverse as peptides (e.g., glucagon, neuropeptides), lipids (e.g., prostaglandins), nucleosides and nucleotides (e.g., adenosine), and amines (e.g., catecholamines, serotonin). These receptors do not interact directly with their respective downstream effector (i.e., an ion channel and/or an enzyme that synthesizes a second messenger); rather, they control one or several target systems via the activation of an intermediary guanine nucleotide‐binding regulatory protein or G protein. G proteins serve as signal transducers, linking extracellularly oriented receptors to membrane‐bound effectors. Traffic in these pathways is regulated by a GTP (on)‐GDP (off) switch, which is regulated by the receptor. The combination of classical biochemistry and recombinant DNA technology has resulted in the discovery of many members of the G protein family. These approaches, complemented in particular by electrophysiological experiments, have also identified several effectors that are regulated by G proteins. We can safely assume that current lists of G proteins and the functions that they control are incomplete.— Freissmuth, M.; Casey, P. J.; Gilman, A. G. G proteins control diverse pathways of transmembrane signaling.FASEB J.3: 2125‐2131; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2546847

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

This article describes ways in which receptors, key components of signal propagation through a synapse, can mediate changes in that propagation. Changes occur at four levels: in the signal‐transducing capability of a single receptor molecule, in the number of receptors per cell, in the subcellular placement of receptor molecules, and in the cytoarchitecture of receptor‐rich regions. The ability of receptors to shift betewen different desired states is called plasticity, and such shifts can be long‐lived as well as transient. In this article we focus on neuronal receptors, although key findings from a variety of cell systems are reported. Neuronal receptor plasticity may have a special role in the assembly as well as the adaptability of the nervous system.— Klein, W. L.; Sullivan, J.; Skorupa, A.; Aguilar, J. S. Plasticity of neuronal receptors.FASEB J.3: 2132‐2140; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2546848

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Polarized epithelial cells perform many critical physiological functions in multicellular organisms. Recent embryological studies of the conversion of nonpolar mesenchymal cells to epithelium in the developing mouse kidney have provided vital information on the molecular mechanisms that initiate epithelial cell polarization. To become polar, the cells first attach to the basement membrane that is produced by the developing epithelial cells themselves. Of the basement membrane components, laminin has a key role in the development of epithelial cell polarity. Laminin is a multidomain glycoprotein composed of three subunits: A, B1, and B2. One binding site for epithelial cells is found in the carboxyl‐terminal part of the A chain of laminin. Antibodies reacting with this part of laminin inhibit polarization of developing epithelial cells in organ cultures of embryonic kidneys. Expression studies also suggest that the A chain of laminin is important for epithelial cell polarization; the A chain appears when the cells begin to polarize, whereas B chains are expressed at an earlier stage of development. The studies of conversion of mesenchyme to epithelium suggest that morphogenesis can be controlled by differential expression of laminin chains.—Ekblom, P. Developmentally regulated conversion of mesenchyme to epithelium.FASEB J.3: 2141‐2150; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2666230

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Therasproteins belong to a family of related polypeptides that are present in all eukaryotic organisms from yeast to human. Their extraordinary evolutionary conservation suggests that they have essential cellular functions, although their exact role remains unknown. Mutations in specific amino acids and overexpression of normal proteins have been linked to altered proliferation and/or differentiation and, particularly, to neoplastic processes. Maturerasproteins are located on the inner side of the plasma membrane, and their biochemical properties include binding and exchange of guanine nucleotides and GTPase activity. The favored hypothesis forrasfunction is that these proteins exist in an equilibrium between an inactive conformation (p21 · GDP) and an active conformation (p21 · GTP) in which they are able to interact with their as! yet unknown cellular target or targets. Similarities in cellular location, structure, and biochemistry with other known regulatory (G) proteins suggest that they play a role in transduction of signals from the cell surface. The elucidation of the crystal structure of normal and transformingrasproteins and the identification of cellular proteins that interact directly with them (GAP, CDC25) or suppress some of their biological effects (Krev‐1) have opened new avenues in the search for their elusive cellular targets and in the elucidation of the functional role ofrasgene products.— Santos, E.; Nebreda, A. R. Structural and functional properties ofrasproteins.FASEB J.3: 2151‐2163; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2666231

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

An overview of research in the field of bioenergetics that led to the development of the binding change mechanism for ATP synthesis is presented, with emphasis on research from the author's laboratory. The text follows closely the Rose Award Lecture given at the 1989 meeting of the American Society for Biochemistry and Molecular Biology. Remarkable advances have revealed that the ubiquitous membrane‐bound ATP synthase has unusual composition and properties. The enzyme complex has 1, 2, 3, or 9‐12 copies of eight or more protein subunits. The catalytic sites are located on three copies of an approximately 55‐kDa subunit. It has the strongest positive catalytic cooperativity known for any enzyme. Examples are given of selected experimental results that have provided insights into its mechanism. These include demonstration of the characteristics, location, and function of catalytic and noncatalytic adenine nucleotide binding sites and the incisive information provided by measurement of phosphate oxygen exchanges and distribution of18O in ATP or Piformed by catalysis. Research from various laboratories gives support to the binding change mechanism in which energy from proton translocation serves principally to promote release of tightly bound ATP, with sequential participation of three catalytic sites. Some speculative suggestions about a rotational catalysis and about the different forms assumed by the ATPase are included.— Boyer, P. D. A perspective of the binding change mechanism for ATP synthesis.FASEB J.3: 2164‐2178; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2526771

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Traditionally, the glucocorticoids have been viewed as catabolic hormones. However, with the present knowledge about how the glucocorticoid receptor protein functions in the stimulation of mRNA synthesis, a new view must be accepted: These steroids also have an anabolic function. They are anabolic because they stimulate the de novo synthesis of enzymes of anabolic pathways. In the liver, stimulation of lipogenic enzymes has been shown. These findings suggest that glucocorticoids can increase feed efficiency and thereby play a role in the etiology of obesity.— Berdanier, C. D. Role of glucocorticoids in the regulation of lipogenesis.FASEB J.3: 2179‐2183; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2666232

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

To observe surface topography of microtubules, we have applied scanning tunneling microscopy (STM), which can image metal and semiconductive surfaces with atomic resolution. Isolated microtubules fixed in 0.1% glutaraldehyde in reassembly buffer containing 0.8 M glycerol were imaged in air on a graphite substrate. The presence of microtubules in solution was verified by electron microscopy. At atmospheric pressure and room temperature, STM probing of both freeze‐dried and hydrated microtubules reveals structures approximately 25 nm in width, consisting of longitudinal filaments about 4 nm in width. These structures match electron microscopy images of microtubules and their component protofilaments. Microtubules imaged by STM frequently appear buckled and semiflattened. Top‐view shaded scans show what appear to be individual tubulin subunits within protofilaments. We believe these results represent the first direct STM observation of protein assemblies in which components can be identified. Although the microtubule image resolution described here is no better than that presently obtainable by other techniques (e.g., electron microscopy with freeze‐drying, shadowing, and/or negative staining), it is significant that suitably prepared biomolecules may be sufficiently conductive and stable for STM imaging, which is ultimately capable of atomic resolution. Further development of STM technology, computer‐enhanced image processing, and elucidation of optimal STM sample preparation indicate that STM and related applications will offer unique opportunities for the study of biomolecular surfaces.—Simić‐Krstić, Y.; Kelly, M.; Schneiker, C.; Krasovich, M.; McCuskey, R.; Koruga, D.; Hameroff, S. Direct observation of microtubules with the scanning tunneling microscope.FASEB J.3: 2184‐2188; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2753269

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Human subjects and mice have been found to have a milder progression of muscular dystrophy when the disease is associated with genotypically determined dwarfism. In this paper we describe an experimental test for reducing growth hormone in dystrophic chickens that uses rabbit anti‐chicken growth hormone antiserum (anti‐cGH). Antiserum was injected daily into dystrophic (line 413) male chickens from day 1 to day 8 after hatching. Dystrophic chickens injected with anti‐cGH maintained a significantly higher score in the standardized test for righting ability (P<0.001‐0.051) from 3 to 9‐1/2 wk after hatching when compared with dystrophic controls. The observed prolongation of the functional ability of injected dystrophic animals suggests that growth hormone plays a role in potentiating the symptoms of dystrophy in chickens.—Kurtenbach, E.; Moraes, S. S.; Trocado, M. T.; Lôbo, G. F.; Nascimento, P. S.; Verjovski‐Almeida, S. Beneficial effects of anti‐growth hormone antiserum in avian muscular dystrophy.FASEB J.3: 2189‐2193; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2787765

出版商:Wiley    

年代:1989

数据来源: WILEY

摘要:

Recent in vivo studies have shown that treatments that decrease circulating prolactin (PRL) in rodents result in significant immunosuppression. Our attempts to demonstrate corresponding direct stimulatory effects of PRL on cultured lymphocytes were unsuccessful. However, antibodies against pituitary PRL potently inhibited both murine and human lymphocyte proliferation in response to both T and B cell mitogens. Further studies using IL 2 and IL 4 responsive cell lines (CTLL‐2 and HT‐2) demonstrated that the same anti‐PRL antibodies inhibited the proliferative response to these cytokine growth factors. Thus, antibodies to PRL appear to block an event occurring in the G1 to GS phase transition of these cell lines, which constitutively express growth factor receptors. The inhibitory activity of anti‐PRL antibodies could be adsorbed by addition of purified human PRL or by immobilized PRL on an affinity column. Antibodies to other pituitary hormones were without inhibitory effect on CTLL‐2 cell proliferation. Proliferation of lymphocytes in serum‐free medium was also potently inhibited by anti‐PRL antibodies, suggesting that antibody effects were not due to neutralization of PRL or other factors contained in culture serum supplements. We suggest from these data that a protein with homology to PRL and recognized by these anti‐PRL antibodies is produced by lymphocytes and plays a critical role in their progression through the cell cycle.—Hartmann, D. P.; Holaday, J. W.; Bernton, E. W. Inhibition of lymphocyte proliferation by antibodies to prolactin.FASEB J, 3: 2194‐2202; 1989.

ISSN:0892-6638    

DOI:10.1096/fasebj.3.10.2787766

出版商:Wiley    

年代:1989

数据来源: WILEY