共查询到20条相似文献,搜索用时 31 毫秒
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Zhang ZG Lambert CA Servotte S Chometon G Eckes B Krieg T Lapière CM Nusgens BV Aumailley M 《Cellular and molecular life sciences : CMLS》2006,63(1):82-91
The GTP-binding proteins RhoA, Cdc42 and Rac1 regulate the organization and turnover of the cytoskeleton and cell-matrix adhesions,
structures bridging cells to their support, and translating forces, external or generated within the cell. To investigate
the specific requirements of Rho GTPases for biomechanical activities of clonal cell populations, we compared side-by-side
stable lines of human fibroblasts expressing constitutively active (CA) RhoA, Cdc42 or Rac1. There was no marked effect of
any CA GTPase on cell adhesion to different extracellular matrix proteins. Cell spreading was CA Rho GTPase specific and independent
of the extracellular matrix proteins allowing adhesion. Mechanical properties were dramatically restricted by CA RhoA on bi-
and in tri-dimensional surroundings, were boosted by CA Rac1 on bi-dimensional surroundings only, and were not or marginally
affected by CA Cdc42. In conclusion, the action of Rho GTPases appears to depend on the task cells are performing.
Received 12 September 2005; received after revision 5 October 2005; accepted 1 November 2005 相似文献
3.
Hepatocyte growth factor in invasive growth of carcinomas 总被引:2,自引:0,他引:2
Desiderio MA 《Cellular and molecular life sciences : CMLS》2007,64(11):1341-1354
4.
Trimeric guanine nucleotide-binding proteins (G proteins) function as the key regulatory elements in a number of transmembrane
signaling cascades where they convey information from agonist-activated receptors to effector molecules. The subcellular localization
of G proteins is directly related to their functional role, i.e., the dominant portion of the cellular pool of G proteins
resides in the plasma membrane. An intimate association of G protein subunits with the plasma membrane has been well known
for a long time. However, results of a number of independent studies published in the past decade have indicated clearly that
exposure of intact target cells to agonists results in subcellular redistribution of the cognate G proteins from plasma membranes
to the light-vesicular membrane fractions, in internalization from the cell surface into the cell interior and in transfer
from the membrane to the soluble cell fraction (high-speed supernatant), i.e., solubilization. Solubilization of G protein
α subunits as a consequence of stimulation of G protein-coupled receptors (GPCRs) with agonists has also been observed in
isolated membrane preparations. The membrane-cytosol shift of G proteins was detected even after direct activation of these
proteins by non-hydrolyzable analogues of GTP or by cholera toxin-induced ADP-ribosylation. In addition, prolonged stimulation
of GPCRs with agonists has been shown to lead to down-regulation of the relevant G proteins. Together, these data suggest
that G proteins might potentially participate in a highly complex set of events, which are generally termed desensitization
of the hormone response. Internalization, subcellular redistribution, solubilization, and down-regulation of trimeric G proteins
may thus provide an additional means (i.e., beside receptor-based mechanisms) to dampen the hormone or neurotransmitter response
after sustained (long-term) exposure.
Received 31 August 2001; received after revision 31 October 2001; accepted 7 November 2001 相似文献
5.
Targeting of the Akt/PKB kinase to the actin skeleton 总被引:2,自引:0,他引:2
Cenni V Sirri A Riccio M Lattanzi G Santi S de Pol A Maraldi NM Marmiroli S 《Cellular and molecular life sciences : CMLS》2003,60(12):2710-2720
Serine/threonine kinase Akt/PKB intracellular distribution undergoes rapid changes in response to agonists such as Platelet-derived growth factor (PDGF) or Insulin-like growth factor (IGF). The concept has recently emerged that Akt subcellular movements are facilitated by interaction with nonsubstrate ligands. Here we show that Akt is bound to the actin skeleton in in situ cytoskeletal matrix preparations from PDGF-treated Saos2 cells, suggesting an interaction between the two proteins. Indeed, by immunoprecipitation and subcellular fractioning, we demonstrate that endogenous Akt and actin physically interact. Using recombinant proteins in in vitro binding and overlay assays, we further demonstrate that Akt interacts with actin directly. Expression of Akt mutants strongly indicates that the N-terminal PH domain of Akt mediates this interaction. More important, we show that the partition between actin bound and unbound Akt is not constant, but is modulated by growth factor stimulation. In fact, PDGF treatment of serum-starved cells triggers an increase in the amount of Akt associated with the actin skeleton, concomitant with an increase in Akt phosphorylation. Conversely, expression of an Akt mutant in which both Ser473 and Thr308 have been mutated to alanine completely abrogates PDGF-induced binding. The small GTPases Rac1 and Cdc42 seem to facilitate actin binding, possibly increasing Akt phosphorylation.Received 10 September 2003; accepted 25 September 2003 相似文献
6.
Joshi S Guleria RS Pan J Bayless KJ Davis GE Dipette D Singh US 《Cellular and molecular life sciences : CMLS》2006,63(23):2859-2870
Developmental exposure to ethanol impairs fetal brain development and causes fetal alcohol syndrome. Although the cerebellum
is one of the most alcohol-sensitive brain areas, signaling mechanisms underlying the deleterious effects of ethanol on developing
cerebellar granule neurons (CGNs) are largely unknown. Here we describe the effects of in vivo ethanol exposure on neurite formation in CGNs and on the activation of Rho GTPases (RhoA and Rac1), regulators of neurite
formation. Exposure of 7-day-old rat pups to ethanol for 3 h moderately increased blood alcohol concentration (BAC) (∼40 mM)
and inhibited neurite formation and Rac1 activation in CGNs. Longer exposure to ethanol for 5 h resulted in higher BAC (∼80 mM),
induced apoptosis, inhibited Rac1, and activated RhoA. Studies demonstrated a regulatory role of Rho GTPases in differentiation
of cerebellar neurons, and indicated that ethanol-associated impairment of Rho GTPase signaling might contribute to brain
defects observed in fetal alcohol syndrome.
Received 16 July 2006; received after revision 12 September 2006; accepted 13 October 2006 相似文献
7.
Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are a family of 18-kDa enzymes involved in cell growth regulation.
Despite very limited sequence similarity to the PTP superfamily, they display a conserved signature motif in the catalytic
site. LMW-PTP associates and dephosphorylate many growth factor receptors, such as platelet-derived growth factor receptor
(PDGF-r), insulin receptor and ephrin receptor, thus downregulating many of the tyrosine kinase receptor functions that lead
to cell division. In particular, LMW-PTP acts on both growth-factor-induced mitosis, through dephosphorylation of activated
PDGF-r, and on cytoskeleton rearrangement, through dephosphorylation of p190RhoGAP and the consequent regulation of the small
GTPase Rho. LMW-PTP activity is modulated by tyrosine phosphorylation on two specific residues, each of them with specific
characteristics. LMW-PTP activity on specific substrates depends also on its localization. Moreover, LMW-PTP is reversibly
oxidized during growth factor signaling, leading to inhibition of its enzymatic activity. Recovery of phosphatase activity
depends on the availability of reduced glutathione and involves the formation of an S–S bridge between the two catalytic site
cysteines. Furthermore, studies on the redox state of LMW-PTP in contact-inhibited cells and in mature myoblasts suggest that
LMW-PTP is a general and versatile modulator of growth inhibition.
Received 17 January 2002; received after revision 22 March 2002; accepted 26 March 2002 相似文献
8.
Spatiotemporal asymmetric auxin distribution: a means to coordinate plant development 总被引:1,自引:0,他引:1
Tanaka H Dhonukshe P Brewer PB Friml J 《Cellular and molecular life sciences : CMLS》2006,63(23):2738-2754
The plant hormone auxin plays crucial roles in regulating plant growth development, including embryo and root patterning,
organ formation, vascular tissue differentiation and growth responses to environmental stimuli. Asymmetric auxin distribution
patterns have been observed within tissues, and these so-called auxin gradients change dynamically during different developmental
processes. Most auxin is synthesized in the shoot and distributed directionally throughout the plant. This polar auxin transport
is mediated by auxin influx and efflux facilitators, whose subcellular polar localizations guide the direction of auxin flow.
The polar localization of PIN auxin efflux carriers changes in response to developmental and external cues in order to channel
auxin flow in a regulated manner for organized growth. Auxin itself modulates the expression and subcellular localization
of PIN proteins, contributing to a complex pattern of feedback regulation. Here we review the available information mainly
from studies of a model plant, Arabidopsis thaliana, on the generation of auxin gradients, the regulation of polar auxin transport and further downstream cellular events.
Received 10 March 2006; received after revision 26 June 2006; accepted 9 August 2006 相似文献
9.
10.
Growth hormone signal transduction 总被引:1,自引:0,他引:1
Growth hormone (GH) promotes animal growth by stimulating bone and cartilage cell proliferation, and influences carbohydrate and lipid metabolism. Some of these effects are brought about indirectly via somatomedin induction in hepatocytes, others by acting directly on the target cells. In either case, GH first binds to specific receptors on cells to trigger a sequence of biochemical events culminating in a biological response. Recently much has been learnt about the molecular structure of GH receptor, its binding to ligand, and the ensuing signal transduction events. 相似文献
11.
The role of VEGF receptors in angiogenesis; complex partnerships 总被引:6,自引:0,他引:6
Cébe-Suarez S Zehnder-Fjällman A Ballmer-Hofer K 《Cellular and molecular life sciences : CMLS》2006,63(5):601-615
Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development and homeostasis but also have
profound effects on neural cells. VEGFs are predominantly produced by endothelial, hematopoietic and stromal cells in response
to hypoxia and upon stimulation with growth factors such as transforming growth factors, interleukins or platelet-derived
growth factor. VEGFs bind to three variants of type III receptor tyrosine kinases, VEGF receptor 1, 2 and 3. Each VEGF isoform
binds to a particular subset of these receptors giving rise to the formation of receptor homo- and heterodimers that activate
discrete signaling pathways. Signal specificity of VEGF receptors is further modulated upon recruitment of coreceptors, such
as neuropilins, heparan sulfate, integrins or cadherins. Here we summarize the knowledge accumulated since the discovery of
these proteins more than 20 years ago with the emphasis on the signaling pathways activated by VEGF receptors in endothelial
cells during cell migration, growth and differentiation.
Received 15 September 2005; received after revision 11 November; accepted 24 November 2005 相似文献
12.
D. S. Morris S. J. E. Stock J. C. McLachlan 《Cellular and molecular life sciences : CMLS》1996,52(8):757-761
Normal and pathological formation of blood vessels is of considerable interest both in terms of basic scientific processes and clinical applications. Angiogenic events in the adult are likely to represent persistence of developmental mechanisms, and embryos are therefore a suitable experimental model for these processes. Among embryonic tissues, muscle is particularly appropriate for investigation, since it is highly vascularised from early stages. There are a number of competing explanations of how this process is controlled. Bioassays offer advantages over conventional molecular localisation techniques, in that they reveal the presence of active processed forms of the molecules under study, rather than non-processed forms, or non-translated meassages. Using these techniques, we report here that embryonic chick muscle, taken from the stages at which blood vessels are forming, produces an angiogenic activity on the chick chorioallantoic membrane (CAM), and transforms NR6 cells in soft agar. Basic fibroblast growth factor (bFGF) is shown to be angiogenic on the CAM in the same way, and also transforms NR6 cells (NR6 cells lack functional epidermal growth factor/transforming growth factor-a receptors, and are believed to respond only to bFGF in this way). Anti-bFGF removes the transforming activity of the embryonic muscle. We conclude that this represents evidence that embryonic chick muscle is producing an FGF-like molecule which is capable of acting as an angiogenic agent at the appropriate times in development. 相似文献
13.
Sampaio MS Bezerra IP Peçanha FL Fonseca PH Capella MA Lopes AG 《Cellular and molecular life sciences : CMLS》2008,65(19):3093-3099
The lack of Na+,K+-ATPase expression in intercalated cells (IC) is an intriguing condition due to its fundamental role in cellular homeostasis.
In order to better understand this question we compared the activities of Na+,K+-ATPase and Na+-ATPase in two MDCK cell clones: the C11, with IC characteristics, and the C7, with principal cells (PC) characteristics.
The Na+,K+-ATPase activity found in C11 cells is far lower than in C7 cells and the expression of its β-subunit is similar in both cells.
On the other hand, a subset of C11 without α-subunit expression has been found. In C11 cells the Na+-ATPase activity is higher than that of the Na+,K+-ATPase, and it is increased by medium alkalinization, suggesting that it could account for the cellular Na+-homeostasis. Although further studies are necessary for a better understanding of these findings, the presence of Na+-ATPase may explain the adequate survival of cells that lack Na+,K+-ATPase.
Received 09 July 2008; received after revision 03 August 2008; accepted 12 August 2008 相似文献
14.
Stephane R. Gross Connie Goh Then Sin Roger Barraclough Philip S. Rudland 《Cellular and molecular life sciences : CMLS》2014,71(9):1551-1579
The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. 相似文献
15.
Chih-Cheng Chang Shih-Ying Tsai Heng Lin Hsiao-Fen Li Yi-Hsuan Lee Ying Chou Chih-Yu Jen Shu-Hui Juan 《Cellular and molecular life sciences : CMLS》2009,66(19):3193-3205
We previously demonstrated the antiproliferative and antiangiogenic effects of 3-methylcholanthrene (3MC), an aryl-hydrocarbon
receptor (AhR) agonist, in human umbilical vascular endothelial cells (HUVECs). Herein, we unraveled its molecular mechanisms
in inhibiting HUVEC motility. 3MC down-regulated FAK, but up-regulated RhoA, which was rescued by AhR knockdown. It led us
to identify novel AhR binding sites in the FAK/RhoA promoters. Additionally, 3MC increased RhoA activity via suppression of
a negative feedback pathway of FAK/p190RhoGAP. With an increase in membrane-bound RhoA, subsequent stress fiber and focal
adhesion complex formation was observed in 3MC-treated cells, and this was reversed by a RhoA inhibitor and AhR antagonists.
Notably, these compounds significantly reversed 3MC-mediated anti-migration in a transwell assay. The in vitro findings were
further confirmed using an animal model of Matrigel formation in Balb/c mice. Collectively, AhR’s genomic regulation of FAK/RhoA,
together with RhoA activation, is ascribable to the anti-migration effect of 3MC in HUVECs. 相似文献
16.
U. Zangemeister-Wittke R. A. Stahel 《Cellular and molecular life sciences : CMLS》1999,55(12):1585-1598
Small-cell lung cancer (SCLC) is characterized by its initial responsiveness to chemotherapy and the appearance of early metastases. Although combination chemotherapy, in some instances together with radiation, has improved the prognosis of this disease, in most patients SCLC ultimately recurs in a drug-resistant form. Several new strategies for the eradication of SCLC are being explored at the preclinical level. The identification of selective target molecules on the surface of SCLC cells, together with the progress made in antibody engineering, have provided new generations of antibodies and immunoconjugates as well as growth factor antagonists and inhibitors. In addition, recent advances in understanding the biology of SCLC have stimulated new investigations searching to counter the molecular basis underlying the increased proliferation and the apoptosis deficiency of SCLC cells. This can be achieved using antisense oligodeoxynucleotides that repress the expression of growth factor receptors and anti-apoptosis genes, or by gene replacement to compensate for the loss or inactivation of tumor suppressor genes. 相似文献
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Tae-In Kam Youngdae Gwon Yong-Keun Jung 《Cellular and molecular life sciences : CMLS》2014,71(24):4803-4813
Alzheimer’s disease (AD) is the most common neurodegenerative disease. Although a major cause of AD is the accumulation of amyloid-β (Aβ) peptide that induces neuronal loss and cognitive impairments, our understanding of its neurotoxic mechanisms is limited. Recent studies have identified putative Aβ-binding receptors that mediate Aβ neurotoxicity in cells and models of AD. Once Aβ interacts with a receptor, a toxic signal is transduced into neurons, resulting in cellular defects including endoplasmic reticulum stress and mitochondrial dysfunction. In addition, Aβ can also be internalized into neurons through unidentified Aβ receptors and induces malfunction of subcellular organelles, which explains some part of Aβ neurotoxicity. Understanding the neurotoxic signaling initiated by Aβ-receptor binding and cellular defects provide insight into new therapeutic windows for AD. In the present review, we summarize the findings on Aβ-binding receptors and the neurotoxicity of oligomeric Aβ. 相似文献
19.
Signalling roles of mammalian phospholipase D1 and D2 总被引:11,自引:0,他引:11
S. Cockcroft 《Cellular and molecular life sciences : CMLS》2001,58(11):1674-1687
Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine to generate the lipid second messenger, phosphatidate
(PA) and choline. PLD activity in mammalian cells is low and is transiently stimulated upon activation by G-protein-coupled
and receptor tyrosine kinase cell surface receptors. Two mammalian PLD enzymes (PLD1 and PLD2) have been cloned and their
intracellular regulators identified as ARF and Rho proteins, protein kinase Cα as well as the lipid, phosphatidylinositol
[4, 5] bisphosphate (PIP2). I discuss the regulation of these enzymes by cell surface receptors, their cellular localisation and the potential function
of PA as a second messenger. Evidence is presented for a role of PA in regulating the lipid kinase activity of PIP 5-kinase,
an enzyme that synthesises PIP2. A signalling role of phospholipase D via PA and indirectly via PIP2 in regulating membrane traffic and actin dynamics is indicated by the available data.
Received 25 April 2001; received after revision 15 June 2001; accepted 15 June 2001 相似文献
20.
Arianne Monge Naldi Max Gassmann Daniel Bodmer 《Cellular and molecular life sciences : CMLS》2009,66(22):3595-3599
It has recently been shown that the oxygen-regulated factors erythropoietin (Epo) and vascular endothelial growth factor (VEGF)
confer protection on different cells, including neuronal-derived ones. The receptors for Epo and VEGF are widely expressed
in different organs. Since mammalian auditory hair cells can irreversibly be damaged by different agents, we aimed to identify
otoprotective compounds. We focused on the role of Epo and VEGF in the inner ear and review the recent studies. Epo and its
receptor are expressed in the inner ear. In vitro experiments on auditory hair cells showed a protective effect of Epo in
ischemia- and gentamicin-induced hair cell damage. In contrast, an in vivo study using an animal model of noise-induced hearing
loss showed a negative effect of Epo. Also VEGF and its receptors are expressed in the inner ear. Changes in the expression
of VEGF or its receptors have been found in the cochlea after noise exposure, transcranial vibration and diabetic or aged
animals. Until now, there are no studies about a direct effect of VEGF on auditory hair cells in vitro or in vivo. We could
exclude a protective effect of VEGF on gentamicin-induced auditory hair cell damage in vitro. Thus, we conclude that Epo but
not VEGF has a protective effect on auditory hair cell damage at least in vitro. (Part of a multi-author review.) 相似文献