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Pathway Similar (pathway + similar)
Selected AbstractsCharacterization of a novel NCAM ligand with a stimulatory effect on neurite outgrowth identified by screening a combinatorial peptide libraryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Lars C. B. Rřnn Abstract The neural cell adhesion molecule, NCAM, plays a key role in neural development and plasticity mediating cell adhesion and signal transduction. By screening a combinatorial library of synthetic peptides with NCAM purified from postnatal day 10 rat brains, we identified a nonapeptide, termed NCAM binding peptide 10 (NBP10) and showed by nuclear magnetic resonance analysis that it bound the NCAM IgI module of NCAM. NBP10 modulated cell aggregation as well as neurite outgrowth induced specifically by homophilic NCAM binding. Moreover, both monomeric and multimeric forms of NBP10 stimulated neurite outgrowth from primary hippocampal neurons. The neurite outgrowth response to NBP10 was inhibited by a number of compounds previously shown to inhibit neurite outgrowth induced by homophilic NCAM binding, including voltage-dependent calcium channel antagonists, suggesting that NBP10 induced neurite outgrowth by activating a signal transduction pathway similar to that activated by NCAM itself. Moreover, an inhibitor of intracellular calcium mobilization, TMB-8, prevented NBP10-induced neurite outgrowth suggesting that NCAM-dependent neurite outgrowth also requires mobilization of calcium from intracellular calcium stores in addition to calcium influx from extracellular sources. By single-cell calcium imaging we further demonstrated that NBP10 was capable of inducing an increase in intracellular calcium in PC12E2 cells. Thus, the NBP10 peptide is a new tool for the study of molecular mechanisms underlying NCAM-dependent signal transduction and neurite outgrowth, and could prove to be a useful modulator of regenerative processes in the peripheral and central nervous system. [source] Ptc, Smo, Sufu, and the Hedgehog signaling pathway in amphioxusEVOLUTION AND DEVELOPMENT, Issue 6 2009Yushuang Lin SUMMARY The Hedgehog (Hh) signaling pathway regulates many developmental processes both in vertebrates and in invertebrates. However, little is known about this pathway in the cephalochordate amphioxus. In this paper, we focus on the Ptc, Smo, and Sufu homologs in amphioxus, which are the key members of the Hh signaling pathway. Their genomic structures show their comparability with homologs in vertebrates. In situ hybridization reveals that amphioxus Ptc, Smo, and Sufu have similar expression patterns in embryogenesis. They are expressed in the neural plate at early neurula stage, and then down-regulated in dorsal neural ectoderm. During development, their transcripts appear and persist in the notochord, the wall of the head cavity, the epithelium of the pharynx, and the gut. The data show that the expression patterns of these three genes are overlapping with Hh and Gli during the embryonic development in amphioxus. Moreover, injection of amphioxus Hh RNA into zebrafish-fertilized eggs can expand the expression domains of Ptc1 and Nk2.2a, the target genes of the Hh signaling pathway, which is similar to the injection of zebrafish Sonic hh a (zShha) and Sonic hh b (zShhb). Our results suggest that amphioxus may possess a conserved and functional Hh signaling pathway similar to that of vertebrates. [source] ERBB2, TBX2, RPS6KB1, and MYC alterations in breast tissues of BRCA1 and BRCA2 mutation carriersGENES, CHROMOSOMES AND CANCER, Issue 1 2004Camilo Adem Breast cancer risk is greatly increased in women who carry mutations in the BRCA1 or BRCA2 genes. Because breast cancer initiation is different between BRCA1/2 mutation carriers and women who do not carry mutations, it is possible that the mechanism of breast cancer progression is also different. Histopathologic and genetic studies have supported this hypothesis. To test this hypothesis further, we utilized a large cohort of women who underwent therapeutic mastectomy (TM) and contralateral prophylactic mastectomy (PM). From this cohort, we developed case groups of women with a family history of breast cancer with BRCA1/2 deleterious mutations, with unclassified variant alterations, and with no detected mutation and matched these cases with sporadic controls from the same TM and PM cohort. Fluorescence in situ hybridization was performed on paraffin sections by use of dual-color probes for ERBB2/CEP17, MYC/CEP8, TBX2/CEP17, and RPS6KB1/CEP17. All malignant and benign lesions, including putative precursor lesions, were studied. The invasive cancers from deleterious mutation carriers had a higher prevalence of duplication of MYC (P = 0.006) and TBX2 (P = 0.0008) compared to controls and a lower prevalence of ERBB2 amplification (P = 0.011). Coduplication of MYC and TBX2 was common in the in situ and invasive lesions from the deleterious mutation carriers. The odds ratio of having a BRCA1/2 mutation is 31.4 (95% CI = 1.7,569) when MYC and TBX2 are coduplicated but ERBB2 is normal. Unclassified variant carriers/no mutation detected and sporadic controls had a similar prevalence of alterations, suggesting that hereditary patients with no deleterious mutations follow a progression pathway similar to that of sporadic cases. With the exception of one atypical ductal hyperplasia lesion, no putative precursor lesion showed any detectable alteration of the probes tested. There was no significant intratumoral heterogeneity of genetic alterations. Our data confirm that a specific pattern of genomic instability characterizes BRCA1/2 -related cancers and that this pattern has implications for the biology of these cancers. Moreover, our current and previous results emphasize the interaction between phenotype and genotype in BRCA1/2 -related breast cancers and that a combination of morphologic features and alterations of ERBB2, MYC, and TBX2 may better define mechanisms of tumor progression, as well as determine which patients are more likely to carry BRCA1/2 mutations. © 2004 Wiley-Liss, Inc. [source] Endogenous and Exogenous Fibroblast Growth Factor 2 Support Survival of Chick Retinal Neurons by Control of Neuronal Neuronal bcl-xL and bcl-2 Expression Through a Fibroblast Berowth Factor Receptor 1- and Erk-Dependent PathwayJOURNAL OF NEUROCHEMISTRY, Issue 1 2000Laurent Désiré Abstract : Fibroblast growth factor (FGF) 2 is a survival factor for various cell types, including retinal neurons. However, little is understood about the molecular bases of the neuroprotective role of FGF2 in the retina. In this report, FGF2 survival activity was studied in chick retinal neurons subjected to apoptosis by serum deprivation. Exogenous FGF2 supported neuronal survival after serum deprivation and increased neuronal bcl-xL and bcl-2 expression, through binding to its receptor R1 (FGF-R1), and subsequent extracellular signal-regulated kinase (ERK) activation. Endogenous FGF2 was transiently overexpressed after serum deprivation. Its down-regulation by antisense oligonucleotides and blockade of its signaling pathway (binding to FGF-R1, tyrosine phosphorylation, and ERK inhibition) decreased bcl-xL and bcl-2 levels and and enhanced apoptosis, suggesting that endogenous FGF2 supported neuronal survival through a pathway similar to that of exogenous FGF2. This pathway may serve to up-regulate, or maintain, bcl-xL and bcl-2 levels that normally decrease during the onset of apoptosis. Indeed, long-term ERK activation and high bcl-xL levels are necessary for the survival activity of both exogenous and endogenous FGF2. Because FGF2 is upregulated following retinal injury in vivo, we suggest that an injury-stimulated autocrine/paracrine FGF2 loop may serve to maintain high levels of survival proteins, such as Bcl-xL, through ERK activation in retinal neurons. [source] Erythropoiesis and Molecular Mechanisms for Sexual Determination in Malaria ParasitesIUBMB LIFE, Issue 4 2000R. E. L. Paul Abstract Malaria parasites proliferate asexually within the vertebrate host but must undergo sexual reproduction for transmission to mosquitoes and hence infection of new hosts. The developmental pathways controlling gametocytogenesis are not known, but several protein kinases and other putative signal transduction elements possibly involved in this phenomenon have been found in Plasmodium. Recently, another developmental pathway, that of Plasmodium sex determination (male or female), has been shown to be triggered by erythropoiesis in the host. Rapid progress is being made in our understanding of the molecular basis of mammalian erythropoiesis, revealing kinase pathways that are essential to cellular responses triggered by the hormone erythropoietin. Although the molecular mechanisms whereby this hormone modulates the sex ratio of malaria parasites remain to be elucidated, it probably activates, within the parasite, transduction pathways similar to those found in other eukaryotes. Indeed, enzymes belonging to protein kinase families known to be involved in the response of mammalian cells to erythropoietin (such as the mitogen-activated protein kinases) have been identified in P. falciparum gametocytes. Some of these enzymes differ markedly from their mammalian homologs; therefore, identification of the transduction pathways of the parasite that are responsible for its developmental response to erythropoietin opens the way to the development of transmission-blocking drugs based on kinase inhibitors. [source] The fellowship of the hobbit: the fauna surrounding Homo floresiensisJOURNAL OF BIOGEOGRAPHY, Issue 6 2010Hanneke J. M. Meijer Abstract The Late Pleistocene Flores fauna shows a pattern observed on many other islands. It is neither aberrant nor exclusive, but the result of non-random selective forces acting upon an impoverished and disharmonic insular fauna. By comparing the Flores vertebrate fauna with other fossil insular biotas, it is apparent that the evolution of Homo floresiensis is part of a general pattern affecting all the inhabitants of Pleistocene Flores. Vertebrate evolution on Flores appears to have been characterized by phylogenetic continuity, low species richness and a disharmonic fauna. All three aspects stem from the isolated position of the island and have resulted in the distinct morphological characteristics of the Flores fauna. Evidence reviewed herein shows that features exhibited by H. floresiensis, such as small stature, a small brain, relatively long arms, robust lower limbs and long feet, are not unique, but are shared by other insular taxa. Therefore, the evolution of H. floresiensis can be explained by existing models of insular evolution and followed evolutionary pathways similar to those of the other terrestrial vertebrates inhabiting Pleistocene Flores. [source] | ||||||||||