Abstract:
:The N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-OMe (1) analogues for-Thp-Leu-Ain-OMe (2), for-Thp-Leu-Phe-OMe (3), for-Met-Leu-Ain-OMe (4), for-Met-Delta(z)Leu-Phe-OMe (5), for-Met-Lys-Phe-For-Met-Lys-Phe (6), for-Met-Leu-Pheol-COMe (7), and for-Nle-Leu-Phe-OMe (8) have been studied. Some of these have been found selective towards the activation of different biological responses of human neutrophils. In particular, peptides 2 and 3, which evoke only chemotaxis, are ineffective in enhancing inositol phosphate, as well as cyclic AMP (cAMP) levels. On the contrary, analogues 5 and 7, which induce superoxide anion production and degranulation, but not chemotaxis, significantly increase the levels of the two intracellular messengers, as is the case of the full agonists 1 and 6. The Ca(2+) ionophore A23187 also activates phospholipase C (PLC) and increases the nucleotide levels; when tested in combination with peptide 1 or 5, a supra-additive enhancement of cAMP concentration is obtained. The PLC blocker, U-73122, inhibits the formylpeptide-induced inositol phosphate formation, as well as cAMP increase. Moreover, this drug drastically reduces superoxide anion release triggered by 1 or 5, whereas it inhibits to a much lesser extent neutrophil chemotaxis induced by 1 or 2. Our results suggest that: (i) PLC stimulation is involved in cAMP enhancement by formylpeptides; (ii) the activation of PLC by formylpeptides, in conditions of increased Ca(2+) influx, induces a supra-additive enhancement of the nucleotide; (iii) the inability of pure chemoattractants to significantly alter the PLC activity or cAMP level, differently from full agonists or peptides specific in inducing superoxide anion release, appears as a general property. Thus, the activation of neutrophil PLC seems essential for superoxide anion release, but less involved in the chemotactic response.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Ferretti ME,Nalli M,Biondi C,Colamussi ML,Pavan B,Traniello S,Spisani Sdoi
10.1016/s0898-6568(01)00140-1subject
Has Abstractpub_date
2001-04-01 00:00:00pages
233-40issue
4eissn
0898-6568issn
1873-3913pii
S0898-6568(01)00140-1journal_volume
13pub_type
杂志文章abstract::mTORC2, the mammalian target of rapamycin complex 2 is activated by upstream growth factors, and performs two major functions, phosphorylation of AKT at the serine of 473 and cell cycle-dependent organization of actin cytoskeleton. However, the mechanisms through which mTORC2 is triggered by these signals remain uncle...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.07.008
更新日期:2013-11-01 00:00:00
abstract::Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2017.09.025
更新日期:2018-01-01 00:00:00
abstract::Sphingolipids and their synthetic enzymes have emerged as critical mediators in numerous diseases including inflammation, aging, and cancer. One enzyme in particular, sphingosine kinase (SK) and its product sphingosine-1-phosphate (S1P), has been extensively implicated in these processes. SK catalyzes the phosphorylat...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109875
更新日期:2021-03-01 00:00:00
abstract::This review is intended to discuss recent developments in the molecular pharmacology of the alpha 1-adrenergic receptor (alpha 1-AR) subtypes. After a brief historical development, we will focus on the more contemporary issues having to do with this receptor family. Emphasis will be put on recent data regarding the cl...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/0898-6568(96)00066-6
更新日期:1996-08-01 00:00:00
abstract::Inositol 1,4,5-trisphosphate 5-phosphatase catalyses the dephosphorylation of the phosphate in the 5-position from inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. One particulate and two soluble enzymes were previously described in bovine brain. In this study, we have obtained a precipitating anti...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(90)90082-l
更新日期:1990-01-01 00:00:00
abstract::Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1, TMEM16A). Ano1 is a Ca(2+) activated Cl(-) channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.09.001
更新日期:2014-12-01 00:00:00
abstract::The Integrin-mediated cell adhesion to the extracellular matrix is implicated in the control of proliferation, survival, migration and differentiation of myoblasts. Focal adhesion kinase (FAK) mediates signals from Integrins and plays an essential role in myotube formation. Cdo forms a multiprotein complex that includ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.03.001
更新日期:2011-07-01 00:00:00
abstract::A tight control of the machineries regulating membrane bending and actin dynamics is very important for the generation of membrane protrusions, which are crucial for cell migration and invasion. Protein/protein and protein/phosphoinositides complexes assemble and disassemble to coordinate these mechanisms, the scaffol...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2020.109692
更新日期:2020-09-01 00:00:00
abstract::The small GTPase Rac1 plays a pivotal role in insulin-stimulated glucose uptake in skeletal muscle, which is mediated by GLUT4 translocation to the plasma membrane. However, regulatory mechanisms for Rac1 and its role in the signaling pathway composed of phosphoinositide 3-kinase and the serine/threonine kinase Akt re...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.02.023
更新日期:2013-06-01 00:00:00
abstract::The p53 tumor suppressor protein is a transcription factor activated by phosphorylation of its N-terminus. MDM2, encoded by a p53-activated gene, acts as a negative-feedback regulator of p53 by promoting p53 degradation. Moreover, MDM2 inhibits p53 by binding to and concealing its N-terminal transcription-activating d...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.05.005
更新日期:2015-09-01 00:00:00
abstract::Tribbles 3 homolog (TRB3) is recently identified as a scaffold-like regulator of various signal transducers and has been implicated in several processes including insulin signaling, NF-kappaB signaling, lipid metabolism and BMP signaling. To further understand cellular mechanisms of TRB3 regulation, we performed a yea...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2008.01.010
更新日期:2008-05-01 00:00:00
abstract::IFN-gamma and TNF-alpha are major proinflammatory cytokines implicated in islet beta-cell destruction, which results in type-1 diabetes; however, the underlying mechanism is not clear. Using pancreatic beta-cell line MIN6N8 cells, co-treatment with TNF-alpha and IFN-gamma, but neither cytokine alone, synergistically i...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2005.03.020
更新日期:2005-12-01 00:00:00
abstract::The maintenance of muscle mass is critical for health and issues associated with the quality of life. Over the last decade, extensive progress has been made with regard to our understanding of the molecules that regulate skeletal muscle mass. Not surprisingly, many of these molecules are intimately involved in the reg...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2011.07.013
更新日期:2011-12-01 00:00:00
abstract::Several members of the mitogen-activated protein kinase kinase kinase (MAP3K) family including MEKK3 and TGFbeta-activating kinase (TAK1) play nonredundant roles in activation of the NF-kappaB transcription factor. However, the mechanism by which MEKK3 mediates NF-kappaB signaling is not fully understood. In this repo...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.12.007
更新日期:2008-04-01 00:00:00
abstract::Glucuronyl C5-epimerase (Hsepi) catalyzes the conversion of glucuronic acid to iduronic acid in the process of heparan sulfate biosynthesis. Targeted interruption of the gene, Glce, in mice resulted in neonatal lethality with varied defects in organ development. To understand the underlying molecular mechanisms of the...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.11.010
更新日期:2019-02-01 00:00:00
abstract::We have studied the effects of cholinergic agonists on the rates of insulin release and the concentrations of diacylglycerol (DAG) and intracellular free Ca2+ ([Ca2+]i) in the beta-cell line MIN6. Insulin secretion was stimulated by glucose, by glibenclamide and by bombesin. In the presence of glucose, both acetylchol...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90038-n
更新日期:1993-11-01 00:00:00
abstract::Proliferation of vascular smooth muscle cells (VSMCs) plays key roles in the progression of intimal hyperplasia, but the molecular mechanisms that trigger VSMC proliferation after vascular injury remain unclear. c-Ski, a co-repressor of transforming growth factor β (TGF-β)/Smad signaling, was detected to express in VS...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2012.09.001
更新日期:2013-01-01 00:00:00
abstract::In humans, thromboxane (TX) A₂ signals through the TPα and TPβ isoforms of its G-protein coupled TXA₂ receptor (TP) to mediate a host of (patho)physiologic responses. Herein, angio-associated migratory cell protein (AAMP) was identified as a novel interacting partner of both TPα and TPβ through an interaction dependen...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2010.12.003
更新日期:2011-04-01 00:00:00
abstract::The attachment of spindle microtubules to kinetochores is crucial for accurate segregation of chromosomes to daughter cells during mitosis. While a growing number of proteins involving this step are being identified, its molecular mechanisms are still not clear. Here we show that protein kinase C zeta (PKCzeta) is loc...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2006.05.017
更新日期:2006-12-01 00:00:00
abstract::Since its discovery in biopsies from breast cancer patients, the effect of corticotropin-releasing hormone (CRH) on carcinoma progression is still unclear. Transforming growth factorβ1 (TGFβ1) promotes Epithelial-Mesenchymal Transition (EMT) and induces Snail1 and Twist1 expressions. Loss of epithelial cadherin (E-cad...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.12.017
更新日期:2014-04-01 00:00:00
abstract::The ectodomain of TOLL-like receptors (TLR) is highly glycosylated with several N-linked gylcosylation sites located in the inner concave surface. The precise role of these sugar N-glycans in TLR receptor activation is unknown. Recently, we have shown that Neu1 sialidase and not Neu2, -3 and -4 forms a complex with TL...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.09.038
更新日期:2010-02-01 00:00:00
abstract::Cellular growth and glucose uptake are regulated by multiple signals generated by the insulin receptor. The mechanisms of individual modulation of these signals remain somewhat elusive. We investigated the role of CaMKII in insulin signalling in a rat skeletal muscle cell line, demonstrating that CaMKII modulates the ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.01.022
更新日期:2009-05-01 00:00:00
abstract::Protein kinase CK2 is a highly conserved, pleiotropic, protein serine/threonine kinase that is essential for life in eukaryotes. CK2 has been implicated in diverse cellular processes such as cell cycle regulation, circadian rhythms, apoptosis, transformation and tumorigenesis. In addition, there is increasing evidence...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2005.07.008
更新日期:2006-03-01 00:00:00
abstract::The involvement of cytosolic phospholipase A(2) (cPLA(2)) and ceramide in the accumulation of cholesteryl ester induced by the uptake of oxidized low-density lipoproteins (oxLDL) in macrophages was investigated. Uptake of oxLDL by [(3)H]oleic acid-labeled macrophages stimulated the formation of cholesteryl oleate, and...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(02)00014-1
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Chemoresistance is one of the main obstacles in the therapy of human cancers, including colorectal cancer (CRC). Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (lncRNA HAND2-AS1) has been demonstrated to be associated with CRC. However, the function of HAND2-AS1 in 5-Fluor...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109483
更新日期:2020-02-01 00:00:00
abstract::Signal transducer and activator of transcription 1 (STAT1) is an important mediator for cytokine signal transduction, particularly IFN-γ. Following IFN-γ stimulation, STAT1 is activated through tyrosine phosphorylation. Little is known about the function and regulation of STAT1 dephosphorylation after activation. We s...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.04.003
更新日期:2011-08-01 00:00:00
abstract::Photodamage in chronically sun-exposed skin manifests clinically as deep wrinkles and histologically as extensive remodelling of the dermal extracellular matrix (ECM) and in particular, the elastic fibre system. We have shown previously that loss of fibrillin microfibrils, a key elastic fibre component, is a hallmark ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.11.024
更新日期:2019-02-01 00:00:00
abstract::Signal transducer and activator of transcription 6 (Stat6) is critical in Th2 polarization of immune cells and active Stat6 activity has been suggested in anti-tumor immunity in animal models. The present study aims at investigating the impact of natural Stat6 activity on tumor microenvironment in human colorectal can...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.11.005
更新日期:2012-03-01 00:00:00
abstract::As a revolutionary gene editing tool based on the adaptive immune defense mechanism of bacteria and archaea against exogenous DNA invasion, CRISPR/Cas system shows many remarkable characteristics over ZFNs and TALENs. However, off-target effect remains as one of the major imperfection of CRISPR/Cas system, hindering i...
journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2020.109577
更新日期:2020-06-01 00:00:00
abstract::We report here a direct modulation by mast cell tryptase of endothelial barrier function through activation of proteinase-activated receptor-2 (PAR-2). In cultured bovine aortic endothelial cells (BAECs), tryptase, trypsin and PAR-2 activating peptide impaired the barrier function as determined by the permeability of ...
journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/s0898-6568(03)00014-7
更新日期:2003-08-01 00:00:00