共查询到20条相似文献,搜索用时 15 毫秒
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Sjöblom B Salmazo A Djinović-Carugo K 《Cellular and molecular life sciences : CMLS》2008,65(17):2688-2701
Alpha-actinin is a cytoskeletal actin-binding protein and a member of the spectrin superfamily, which comprises spectrin, dystrophin and their homologues and isoforms. It forms an anti-parallel rod-shaped dimer with one actin-binding domain at each end of the rod and bundles actin filaments in multiple cell-type and cytoskeleton frameworks. In non-muscle cells, alpha-actinin is found along the actin filaments and in adhesion sites. In striated, cardiac and smooth muscle cells, it is localized at the Z-disk and analogous dense bodies, where it forms a lattice-like structure and stabilizes the muscle contractile apparatus. Besides binding to actin filaments alpha-actinin associates with a number of cytoskeletal and signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, rendering it important structural and regulatory roles in cytoskeleton organization and muscle contraction. This review reports on the current knowledge on structure and regulation of alpha-actinin. 相似文献
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C. L. Salanga M. O’Hayre T. Handel 《Cellular and molecular life sciences : CMLS》2009,66(8):1370-1386
Chemokines are small, secreted proteins that bind to the chemokine receptor subfamily of class A G protein-coupled receptors.
Collectively, these receptor-ligand pairs are responsible for diverse physiological responses including immune cell trafficking,
development and mitogenic signaling, both in the context of homeostasis and disease. However, chemokines and their receptors
are not isolated entities, but instead function in complex networks involving homo- and heterodimer formation as well as crosstalk
with other signaling complexes. Here the functional consequences of chemokine receptor activity, from the perspective of both
direct physical associations with other receptors and indirect crosstalk with orthogonal signaling pathways, are reviewed.
Modulation of chemokine receptor activity through these mechanisms has significant implications in physiological and pathological
processes, as well as drug discovery and drug efficacy. The integration of signals downstream of chemokine and other receptors
will be key to understanding how cells fine-tune their response to a variety of stimuli, including therapeutics.
Received 19 October 2008; received after revision 7 November 2008; accepted 11 November 2008
C. L. Salanga, M. O’Hayre: These authors contributed equally. 相似文献
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The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy. 相似文献
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Pratt RF 《Cellular and molecular life sciences : CMLS》2008,65(14):2138-2155
The DD-peptidase enzymes (penicillin-binding proteins) catalyze the final transpeptidation reaction of bacterial cell wall (peptidoglycan) biosynthesis. Although there is now much structural information available about these enzymes, studies of their activity as enzymes lag. It is now established that representatives of two low-molecular-mass classes of DD-peptidases recognize elements of peptidoglycan structure and rapidly react with substrates and inhibitors incorporating these elements. No members of other DD-peptidase classes, including the high-molecular-mass enzymes, essential for bacterial growth, appear to interact strongly with any particular elements of peptidoglycan structure. Rational design of inhibitors for these enzymes is therefore challenging. 相似文献
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Irigoyen M Ansó E Salvo E Dotor de las Herrerías J Martínez-Irujo JJ Rouzaut A 《Cellular and molecular life sciences : CMLS》2008,65(14):2244-2255
TGFbeta-induced protein (TGFBI) is an extracellular protein that mediates cell adhesion to collagen, laminin and fibronectin through its interaction with different beta integrins. We had previously reported that hypoxia-induced TGFBI mRNA expression in lymphatic endothelial cells (LEC). Here, we demonstrate that TGFBI can contribute to hypoxia-induced increases in LEC adhesion to the ECM. We show that while there are no changes in alpha1, alpha4, alphav, beta1, beta2, beta3, alpha5beta1, alphavbeta3, alphavbeta5 integrin expression on the LEC surface after hypoxia exposure, there exists an accumulation of TGFBI adaptor protein in LEC supernatants. We also demonstrate that hypoxia driven TGBFI expression is dependent on TGFbeta production by LEC. Furthermore, we show that TGFBI mediated LEC adhesion and migration through the ECM by its binding to the beta3 integrin. The identification of the specific mechanisms regulating LEC-ECM interactions may help us design new therapeutic applications for diseases in which lymphatic vessel function is compromised. 相似文献
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Smrcka AV 《Cellular and molecular life sciences : CMLS》2008,65(14):2191-2214
G protein betagamma subunits are central participants in G protein-coupled receptor signaling pathways. They interact with receptors, G protein alpha subunits and downstream targets to coordinate multiple, different GPCR functions. Much is known about the biology of Gbetagamma subunits but mysteries remain. Here, we will review what is known about general aspects of structure and function of Gbetagamma as well as discuss emerging mechanisms for regulation of Gbetagamma signaling. Recent data suggest that Gbetagamma is a potential therapeutic drug target. Thus, a thorough understanding of the molecular and physiological functions of Gbetagamma has significant implications. 相似文献
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Chlebova K Bryja V Dvorak P Kozubik A Wilcox WR Krejci P 《Cellular and molecular life sciences : CMLS》2009,66(2):225-235
Fibroblast growth factor 2 (FGF2) is one of the most studied growth factors to date. Most attention has been dedicated to
the smallest, 18kDa FGF2 variant that is released by cells and acts through activation of cell-surface FGF-receptor tyrosine
kinases. There are, however, several higher molecular weight (HMW) variants of FGF2 that rarely leave their producing cells,
are retained in the nucleus and act independently of FGF-receptors (FGFR). Despite significant evidence documenting the expression
and intracellular trafficking of HMW FGF2, many important questions remain about the physiological roles and mechanisms of
action of HMW FGF2. In this review, we summarize the current knowledge about the biology of HMW FGF2, its role in disease
and areas for future investigation.
Received 28 July 2008; received after revision 18 August 2008; accepted 22 August 2008 相似文献
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Abaraviciene SM Lundquist I Salehi A 《Cellular and molecular life sciences : CMLS》2008,65(14):2256-2265
Chronic exposure of pancreatic islets to elevated levels of palmitate leads to beta-cell dysfunction. We examined possible involvement of mitogenactivated protein kinases (MAPKs) and caspase-3 in palmitate-induced beta-cell dysfunction and tested the influence of the anti-diabetic drug rosiglitazone (ROZ). Palmitate amplified glucose-stimulated augmentation of intracellular free calcium ([Ca2+]i) and insulin secretion in incubated islets. ROZ suppressed this amplification, whereas it modestly augmented glucose-induced increase in these events. ROZ suppressed short-term palmitate-induced phosphorylation of pro-apoptotic MAPKs, i.e., SAPK/JNK and p38. Long-term islet culturing with palmitate induced inducible nitric oxide synthase (iNOS) and activated SAPK/JNK-p38. ROZ counteracted these effects. Both palmitate and cytokines activated caspase-3 in MIN6c4-cells and isolated islets. ROZ suppressed palmitate- but not cytokine-induced caspase-3 activation. Finally, after palmitate culturing, ROZ reversed the inhibitory effect on glucose-stimulated insulin release. We suggest that ROZ counteracts palmitateinduced deleterious effects on beta-cell function via suppression of iNOS, pro-apoptotic MAPKs and caspase-3 activities, as evidenced by restoration of glucose-stimulated insulin release. 相似文献
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Myosin I is a non-filamentous, single-headed, actin-binding motor protein and is present in a wide range of species from yeast to man. The role of these class I myosins have been studied extensively in simple eukaryotes, showing their role in diverse processes such as actin cytoskeleton organization, cell motility, and endocytosis. Recently, studies in metazoans have begun to reveal more specialized functions of myosin I. It will be a major challenge in the future to examine the physiological functions of each class I myosin in different cell types of metazoans. 相似文献
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Gene expression in spermiogenesis 总被引:10,自引:0,他引:10
Germ cells convey parental genes to the next generation, and only germ cells perform meiosis, which is a mechanism that preserves the parental genes. The fusion of the products of germ cell meiosis, the haploid sperm and egg, creates the next generation. Sperm are the haploid germ cells that contribute genes to the egg. In preparation for this, the haploid round spermatids produced by meiosis undergo drastic morphological changes to become sperm. During this process of spermiogenesis, the nuclear form of the haploid germ cell takes shape, the mitochondria are rearranged in a specific manner, the flagellum develops and the acrosome forms. Spermatogenesis is supported by precise and orderly regulation of gene expression during the changes in chromatin structure, when protamine replaces histone. In this report, we summarize the molecular mechanisms involved in spermiogenesis.Received 2 September 2004; received after revision 7 October 2004; accepted 7 October 2004 相似文献
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Eukaryotic genomes have complex spatial organization in the nucleus. The factors and the mechanisms involved in this organization
remain an enigma. Among the many proteins implicated in such a role, the ubiquitous Zn-finger protein CTCF stands out. Here
we summarize the evidence placing CTCF in the enviable position of a master organizer of the genome. CTCF can form loops in cis, and can bridge sequences located on different chromosomes in trans. The thousands of CTCF binding sites, identified in recent genome-wide localization studies, and their distribution along
the genome further support a crucial role of CTCF as a chromatin organizer.
Received 10 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
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Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease. 相似文献
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Lin CI Chen CN Huang MT Lee SJ Lin CH Chang CC Lee H 《Cellular and molecular life sciences : CMLS》2008,65(17):2740-2751
Lysophosphatidic acid (LPA) is a low-molecular-weight lipid growth factor, which binds to G-protein-coupled receptors. Previous studies have shown that LPA enhances vascular endothelial growth factor-A (VEGF-A) expression in cancer cells and promotes angiogenesis process. However, the roles of LPA in lymphatic vessel formation and lymphangiogenesis have not been investigated. Here, we demonstrated that LPA up-regulated VEGF-C mRNA and protein expressions in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression levels of lymphatic markers, including Prox-1, LYVE-1 and podoplanin, were enhanced in LPA-stimulated tube forming endothelial cells in vitro and in vivo. Moreover, we showed that pretreatment with MAZ51, a VEGFR-3 kinase inhibitor, and introduction of VEGFR-3 siRNA suppressed LPA-induced HUVEC tube formation and lymphatic marker expressions. These results demonstrated that LPA enhances expression of lymphatic markers through activating VEGF-C receptors in endothelial cells. This study provides basic information that LPA might be a target for therapeutics against lymphangiogenesis and tumor metastasis. 相似文献
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The epo genes of many teleosts, including zebrafish, have been cloned following the first identification of nonmammalian EPO
from fugu in 2004. The zebrafish (Danio rerio) animal model is well suited for both developmental and genetic analyses for
studying vertebrate erythropoiesis. The purpose of this review is to provide an update of recent progress in research on teleost
EPO with a focus on its structure, expression and secretion. The EPO receptor and the downstream JAK/STAT signaling pathway
are also discussed.
Received 29 April 2008; received after revision 23 June 2008; accepted 25 June 2008 相似文献
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J. Kim D. C. Han J. M. Kim S. Y. Lee S. J. Kim J. R. Woo J. W. Lee S.-K. Jung K. S. Yoon H. G. Cheon S. S. Kim S. H. Hong B.-M. Kwon 《Cellular and molecular life sciences : CMLS》2009,66(10):1766-1781
Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals
that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis
showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte
cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2
in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated
by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte
cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte
cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological
responses of the ligands.
Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009 相似文献