Abstract：
:Epidermal growth factor receptor (EGFR) ligands undergo a complex series of processing events during their maturation to active signaling proteins. Like its mammalian homologs, the predominant Drosophila EGFR ligand Spitz is produced as a transmembrane pro-protein. In the secretory pathway, Spitz is cleaved within its transmembrane domain to release the extracellular signaling domain. This domain is modified with an N-terminal palmitate group that tethers it to the plasma membrane. We found that the pro-protein can reach the cell surface in the absence of proteolysis, but that it fails to activate the EGFR. To address why the transmembrane pro-protein is inactive, whereas membrane association through the palmitate group promotes activity, we generated a panel of chimeric constructs containing the Spitz extracellular region fused to exogenous transmembrane proteins. Although the orientation of the EGF domain and its distance from the plasma membrane varies in these chimeras, they are all active in vivo. Thus, tethering Spitz to the membrane via a transmembrane domain at either terminus does not prevent activity. Conversely, removing the N-terminal palmitate group from the C-terminally tethered pro-protein does not render it active. Furthermore, we show that the Spitz transmembrane pro-protein can activate the EGFR in a tissue culture assay, indicating that its failure to signal in vivo is not due to structural features. In polarized imaginal disc cells, unprocessed Spitz pro-protein localizes to apical puncta, whereas the active chimeric Spitz constructs are basolaterally localized. Taken together, our data support the model that localized trafficking of the pro-protein restricts its ability to activate the receptor in polarized tissues.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Steinhauer J,Liu HH,Miller E,Treisman JEdoi
10.1242/jcs.131169subject
Has Abstractpub_date
2013-10-01 00:00:00pages
4469-78issue
Pt 19eissn
0021-9533issn
1477-9137pii
jcs.131169journal_volume
126pub_type
杂志文章abstract：:BMP-dependent patterning in the Drosophila melanogaster wing imaginal disc serves as a paradigm to understand how morphogens specify cell fates. The observed profile of the transcriptional response to the graded signal of BMP relies upon two counter-active gradients of pMad and Brinker (Brk). This patterning model is ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.110569
更新日期：2012-12-01 00:00:00
abstract：:The notion that cell shape and spreading can regulate cell proliferation has evolved over several years, but only recently has this been linked to forces from within and upon the cell. This emerging area of mechanical signaling is proving to be wide-spread and important for all cell types. The microenvironment that su...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.067009
更新日期：2011-04-15 00:00:00
abstract：:Eukaryotic cells replicate and partition their organelles between the mother cell and the daughter cell at cytokinesis. Polarized cells, notably the budding yeast Saccharomyces cerevisiae, are well suited for the study of organelle inheritance, as they facilitate an experimental dissection of organelle transport and r...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.151423
更新日期：2015-02-15 00:00:00
abstract：:The 5T4 oncofoetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:In metazoans, cyclin-dependent kinase 7 (CDK7) has essential roles in both the cell-division cycle and transcription, as a CDK-activating kinase (CAK) and as a component of the general transcription factor TFIIH, respectively. Controversy over its double duty has been resolved, but questions remain. First, how does CD...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.02718
更新日期：2005-11-15 00:00:00
abstract：:A new mouse model has been developed to study the localisation and trafficking of the glucose transporter GLUT4 in muscle. The mouse line has specific expression of a GFP and HA-epitope-tagged version of GLUT4 under the control of a muscle-specific promoter. The exofacial HA-tag has enabled fluorescent labelling of on...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.041178
更新日期：2009-03-01 00:00:00
abstract：:The endoplasmic reticulum-Golgi intermediate compartment (ERGIC) defined by the cycling lectin ERGIC-53 consists of tubulovesicular clusters, but it is unknown if these membranes are transport vehicles or stationary entities. Here, we show by live imaging that GFP-ERGIC-53 mainly localizes to long-lived stationary and...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01615
更新日期：2005-01-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.120477
更新日期：2013-08-15 00:00:00
abstract：:Addition of lysophosphatidic acid (LPA) to serum-deprived N1E-115 neuronal cells results in rapid f-actin assembly accompanied by neurite retraction and rounding of the cell body due to contraction of the cortical actin cytoskeleton. LPA action is mimicked by activated RhoA, while it is blocked by dominant-negative Rh...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:Protein kinase CK2, a vital, pleiotropic and highly conserved serine/threonine phosphotransferase is involved in transcription-directed signaling, gene control and cell cycle regulation and is suspected to play a role in global processes. Searching for these global roles, we analyzed the involvement of CK2 in gene exp...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00352
更新日期：2003-04-15 00:00:00
abstract：:The protein product of the gene responsible for ocular albinism type 1, named OA1, is a pigment-cell-specific membrane glycoprotein, displaying features of G-protein-coupled receptors, yet exclusively localized to late endosomes, lysosomes and melanosomes. To dissect the signals responsible for the intracellular local...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02930
更新日期：2006-05-15 00:00:00
abstract：:The functions of polycomb products extend beyond their well-known activity as transcriptional regulators to include genome duplication processes. Polycomb activities during DNA replication and DNA damage repair are unclear, particularly without induced replicative stress. We have used a cellular model of conditionally...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.173021
更新日期：2015-10-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Using L cells expressing one of three functional E-cadherin constructs, the wild-type, a chimeric molecule with alpha-catenin (EalphaC), and a tail-less one, we determined the effect of v-Src expression on E-cadherin-mediated adhe...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.136176
更新日期：2013-12-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.188060
更新日期：2017-01-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:The presence of an acetolysis-resistant polymer (sporopollenin) in the cellular slime moulds is demonstrated. This polymer is located on the stalk sheath of fruiting bodies as a bundle of fine fibrils (4-5 nm diameter). The location and structure of sporopollenin in spores are shown to vary considerably, depending upo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.009977
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：2001-05-01 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：2002-01-01 00:00:00
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journal_title：Journal of cell science
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更新日期：2012-08-15 00:00:00
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journal_title：Journal of cell science
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doi：
更新日期：1988-10-01 00:00:00
abstract：:An electron-microscopic study of various fractions taken during a newly developed method for preparation of brush border vesicles from rat duodenum, has shown that vesiculation of microvilli can occur in situ on the brush border membrane. This mode of formation ensures that the vesicle membranes are oriented as in viv...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:Genomes exist in vivo as complex physical structures, and their functional output (i.e. the gene expression profile of a cell) is related to their spatial organization inside the nucleus as well as to local chromatin status. Chromatin modifications and chromosome conformation are distinct in different tissues and cell...
journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章,评审
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更新日期：2016-03-15 00:00:00
