Abstract：
:Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGF-like domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane pro-form from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HB-EGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Prince RN,Schreiter ER,Zou P,Wiley HS,Ting AY,Lee RT,Lauffenburger DAdoi
10.1242/jcs.058321subject
Has Abstractpub_date
2010-07-01 00:00:00pages
2308-18issue
Pt 13eissn
0021-9533issn
1477-9137pii
jcs.058321journal_volume
123pub_type
杂志文章abstract：:The position of the nucleus is regulated in different developmental stages and cellular events. During polarization, the nucleus moves away from the future leading edge and this movement is required for proper cell migration. Nuclear movement requires the LINC complex components nesprin-2G and SUN2, which form transme...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.087049
更新日期：2012-03-01 00:00:00
abstract：:The large GTPase dynamin, long known for its role in endocytosis, has most recently been implicated as a facilitator of cell migration and invasion. Recent observations link dynamin to the cycle of membrane expansion and retraction essential for cell motility. Its role in actin polymerization, membrane deformation and...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.02963
更新日期：2006-05-01 00:00:00
abstract：:The mammalian inactive X chromosome (Xi) is a model for facultative heterochromatin. Increased DNA compaction for the Xi, and for facultative heterochromatin in general, has long been assumed based on recognition of a distinct Barr body using nucleic-acid staining. This conclusion has been challenged by a report revea...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.026104
更新日期：2008-04-01 00:00:00
abstract：:Transglutaminases (TGases) are enzymes which catalyze cross-link formation between glutamine residues and lysine residues in substrate proteins. In the present study, we report for the first time that a representative enzyme, blood coagulation factor XIIIa (FXIIIa), is capable of mediating adhesion of various cells. W...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:Megalin is a receptor expressed by embryonic epithelia that mediates endocytosis of numerous ligands, including sonic hedgehog (Shh) and retinol, the precursor to retinoic acid (RA). The importance of Shh and RA signaling in neurodevelopment, combined with the fact that megalin-deficient mice show profound neurodevelo...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00313
更新日期：2003-03-15 00:00:00
abstract：:The cross-striated muscle from the heart ventricle and the smooth penis retractor muscle of the freshwater snail Lymnaea stagnalis have been investigated by X-ray microanalysis to establish whether lanthanum can cross the plasma membrane, as has been reported by other investigators. Tissues were incubated in 1 mM ioni...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1985-04-01 00:00:00
abstract：:Human SW-13 cells express the intermediate filament protein vimentin in a mosaic pattern (Hedberg, K. K. and Chen, L. B. (1986). Exp. Cell Res. 163, 509-517). We have isolated SW-13 clones that do (vim+) or do not (vim-) synthesize vimentin as analyzed using anti-intermediate filament immunofluorescence, electron micr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:MOR1, the Arabidopsis thaliana homologue of the Xenopus microtubule-associated protein MAP215, is required for spatial organization of the acentrosomal microtubule arrays of plant cells. To determine how loss of MOR1 function affects microtubule dynamics, we compared various parameters of microtubule dynamics in the t...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.039065
更新日期：2008-12-15 00:00:00
abstract：:Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli and strongly implicated in the control of integrin-mediated cell adhesion. Recent evidence indicates that Rap1 also plays a key role in formation of cadherin-based cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.03306
更新日期：2007-01-01 00:00:00
abstract：:Schizosaccharomyces pombe cells divide by medial fission throughout contraction of an actomyosin ring and deposition of a multilayered division septum that must be cleaved to release the two daughter cells. Although many studies have focused on the actomoysin ring and septum assembly, little information is available c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00377
更新日期：2003-05-01 00:00:00
abstract：:Small latent TGF-beta consists of latency associated peptide (LAP) bound to the 25 kDa TGF-beta by noncovalent interactions. Small latent TGF-beta is secreted from cells and deposited into the extracellular matrix as covalent complexes with its binding proteins, LTBPs. Four LTBPs have been molecularly cloned and their...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-08-01 00:00:00
abstract：:The current paradigm of noncanonical NF-κB signaling suggests that the loss of TRAF2, TRAF3 or cIAP1 and cIAP2 leads to stabilization of NF-κB-inducing kinase (NIK) to activate the noncanonical pathway. Although a crucial role of RIP1 in the TNFα-induced canonical NF-κB pathway has been well established, its involveme...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.075770
更新日期：2011-02-15 00:00:00
abstract：:A correlation between intranuclear distribution of large tumor antigen (T-ag) and proliferative activity in Simian virus 40 (SV40)-transformed cells has been established. Nuclear T-ag was cytochemically detected by the immunoperoxidase reaction. Cell populations with a high growth rate displayed a heterogeneous patter...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:Previous investigators have examined mitochondrial DNA (mtDNA) in the electron microscope (EM) after extraction from mitochondria and rotary shadowing. We have observed mtDNA in situ by the osmiumammine procedure for specific staining of DNA in the EM. The procedure was modified to improve the regularity of the staini...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
abstract：:We investigated the relative contributions of phagocytosis and plasma membrane transport to the uptake of amino acids and a protein (egg albumin) in amounts which allow Tetrahymena thermophila to grow and multiply. We used a mutant capable of indefinite growth without food vacuole formation (phagocytosis) and its wild...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-04-01 00:00:00
abstract：:Syntaxin 1C (STX1C), produced by alternative splicing of the stx1A gene, is a soluble syntaxin lacking a SNARE domain and a transmembrane domain. It is unclear how soluble syntaxin can control intracellular membrane trafficking. We found that STX1C affected microtubule (MT) dynamics through its tubulin-binding domain ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.081943
更新日期：2012-02-15 00:00:00
abstract：:A key step in cell migration is the dynamic formation and disassembly of adhesions at the front and the concomitant movement and release of adhesions in the rear of the cell. Fibroblasts maintained in the absence of serum have stable adhesions within the rear of the cell and exhibit reduced trailing-edge retraction re...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.020941
更新日期：2008-03-15 00:00:00
abstract：:Smooth muscle cells may be isolated from the taenia coli muscle of the guinea pig which, when made permeable by treatment with Triton X-100 (0-05%) show a sensitivity to Ca for contraction with MgATP. The rate of contraction, about 10 micron s-1, corresponds closely to the maximum velocity of shortening of the intact ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-04-01 00:00:00
abstract：:Microscopic green algae inhabiting desert microbiotic crusts are remarkably diverse phylogenetically, and many desert lineages have independently evolved from aquatic ancestors. Here we worked with five desert and aquatic species within the family Scenedesmaceae to examine mechanisms that underlie desiccation toleranc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.212233
更新日期：2018-04-10 00:00:00
abstract：:Xenopus egg extracts, which support nuclear assembly and DNA replication, were functionally depleted of lamin LIII by inoculating them with monoclonal anti-lamin antibodies. Phase-contrast microscopy and electron-microscopy studies indicated that lamin-depleted extracts supported efficient chromatin decondensation, an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:To optimally perform the diversity of metabolic functions that occur within peroxisomes, cells must dynamically regulate peroxisome size, number and content in response to the cell state and the environment. Except for transcriptional regulation little is known about the mechanisms used to perform this complicated fea...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.195255
更新日期：2016-11-01 00:00:00
abstract：:In neutrophils and other phagocytic cells, the small GTPase Rac is an essential regulator of a multi-component NADPH oxidase that produces high levels of superoxide, which kills invading pathogens. In many other cell types, Rac and newly discovered relatives of the neutrophil burst oxidase and its subunits have been f...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00937
更新日期：2004-01-15 00:00:00
abstract：:As a contribution to the understanding of the mechanism of the collective motion of the cell mass in the migrating pseudoplasmodium its motive force has been determined. The measurements in the present paper were made by an original method using centrifugal force. The maximum value of the motive force of a migrating p...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1982-08-01 00:00:00
abstract：:The conversion of the cellular prion protein (PrPc) into a pathogenic isoform (PrP(Sc)) is one of the underlying events in the pathogenesis of the fatal transmissible spongiform encephalopathies (TSEs). Numerous compounds have been described to inhibit prion replication and PrP(Sc) accumulation in cell culture. Among ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02609
更新日期：2005-11-01 00:00:00
abstract：:In a wild population of the American newt Notophthalmus viridescens 15 females out of a total of 94 were found to be heterozygous for a paracentric inversion which includes almost the whole of the longer arm of the smallest chromosome (XI). The inversion was recognized in preparations of lampbrush chromosomes because ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-04-01 00:00:00
abstract：:RAS isoforms have been proposed to exhibit differing biological outputs due to differences in their relative occupancy of cellular organelles and signalling microdomains. The membrane binding and targeting motifs of RAS are encoded by the C-terminal hypervariable region (HVR), and the precise localisation depends upon...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.020107
更新日期：2008-02-15 00:00:00
abstract：:Cornichon proteins are structurally related transmembrane proteins that have been studied in and Drosophila and yeast. In Drosophila, Cornichon (Cni) is involved in embryo polarization by the TGFalpha-related Gurken. In yeast, the Cni-related Erv14 is required for axial budding. A cargo receptor function has been prop...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.004200
更新日期：2007-07-15 00:00:00
abstract：:Cyclin G (CycG) belongs to the atypical cyclins, which have diverse cellular functions. The two mammalian CycG genes, CycG1 and CycG2, regulate the cell cycle in response to cell stress. Detailed analyses of the role of the single Drosophila cycG gene have been hampered by the lack of a mutant. We generated a null mut...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.113902
更新日期：2012-11-15 00:00:00
abstract：:Circadian rhythms regulate a wide variety of physiological and metabolic processes. The clock machinery comprises complex transcriptional-translational feedback loops that, through the action of specific transcription factors, modulate the expression of as many as 10% of cellular transcripts. This marked change in gen...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.051649
更新日期：2010-11-15 00:00:00
abstract：:Vascular endothelial (VE)-cadherin is the endothelium-specific member of the cadherin family of homotypic cell adhesion molecules. VE-cadherin, but not the cell adhesion molecule platelet/endothelial cell adhesion molecule (PECAM-1), markedly colocalizes with actin stress fibers at cell-cell junctions between human um...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-06-01 00:00:00
