Abstract：
:In many epithelial cells, epidermal growth factor (EGF) augments the epithelial-mesenchymal transition (EMT) that occurs when cells are treated with transforming growth factor β (TGFβ). We demonstrate that this augmentation requires activation of SH2 domain-containing phosphatase-2 (SHP2; also known as PTPN11), a proto-oncogene. In lung and pancreatic cancer cell lines, reductions in E-cadherin expression, increases in vimentin expression and increases in cell scatter rates were larger when cells were treated with TGFβ and EGF versus TGFβ or EGF alone. SHP2 knockdown promoted epithelial characteristics basally and antagonized EMT in response to TGFβ alone or in combination with EGF. Whereas EGF promoted SHP2 binding to tyrosine phosphorylated GAB1, which promotes SHP2 activity, TGFβ did not induce SHP2 association with phosphotyrosine-containing proteins. Knockdown of endogenous SHP2 and reconstitution with an SHP2 mutant with impaired phosphotyrosine binding ability eliminated the EGF-mediated EMT augmentation that was otherwise restored with wild-type SHP2 reconstitution. These results demonstrate roles for basal and ligand-induced SHP2 activity in EMT and further motivate efforts to identify specific ways to inhibit SHP2, given the role of EMT in tumor dissemination and chemoresistance.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Buonato JM,Lan IS,Lazzara MJdoi
10.1242/jcs.169599subject
Has Abstractpub_date
2015-11-01 00:00:00pages
3898-909issue
21eissn
0021-9533issn
1477-9137pii
jcs.169599journal_volume
128pub_type
杂志文章abstract：:MACF (microtubule actin cross-linking factor) is a large, 608-kDa protein that can associate with both actin microfilaments and microtubules (MTs). Structurally, MACF can be divided into 3 domains: an N-terminal domain that contains both a calponin type actin-binding domain and a plakin domain; a rod domain that is co...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Microinjected GTP gamma S revealed three distinct steps in the exocytic transport of the temperature sensitive glycoprotein of vesicular stomatitis virus (ts-O45-G) from the ER to the cell surface in intact Vero cells. While COPII dependent export of ts-O45-G from the ER is blocked in cells injected with recombinant p...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
abstract：:Targeting of the NG2 proteoglycan to cellular retraction fibers was studied by expressing mutant NG2 molecules lacking specific structural elements of the proteoglycan. Both the cytoplasmic domain and the chondroitin sulfate chain of NG2 appear to have roles in sorting NG2 to subcellular microdomains destined to becom...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
abstract：:Current methodologies for targeting the mitochondrial genome for research and/or therapy development in mitochondrial diseases are restricted by practical limitations and technical inflexibility. A molecular toolbox for CRISPR-mediated mitochondrial genome editing is desirable, as this could enable targeting of mtDNA ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.248468
更新日期：2020-09-16 00:00:00
abstract：:Programmed cell death comprises several subtypes, as revealed by electron microscopy. Apoptosis or type I programmed cell death is characterized by condensation of cytoplasm and preservation of organelles, essentially without autophagic degradation. Autophagic cell death or type II programmed cell death exhibits exten...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:The detergent-insoluble T. brucei cytoskeleton consists of several morphologically distinct regions and organelles, many of which are detectable only by electron microscopy. We have produced a set of monoclonal antibodies that define each structural component of this highly ordered cytoskeleton. The monoclonal antibod...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:The developmental stage at which Dictyostelium discoideum strain v12/M2 cells was inhibited in resuming cell division was monitored by a Coulter counter. Neither vegetative nor pre-aggregating v12/M2 amoebae used as inocula in liquid growth cultures exhibited a delay in recommencing cell division. Inocula prepared fro...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:The biosynthetic machinery in the melanotrope cells of the Xenopus intermediate pituitary is primarily dedicated to the generation of proopiomelanocortin (POMC)-derived, melanophore-stimulating peptides. Transfer of the animal to a black background stimulates the production of these peptides and causes a dramatic incr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:The neuromuscular junction (NMJ) is the largest, most-complex synapse in the human body. Motor neuron (MN) diseases, such as amyotrophic lateral sclerosis (ALS), specifically target MNs and the NMJs. However, little is known about the reasons for MN-selective neuronal and synaptic vulnerability in MN diseases. Here, u...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.234492
更新日期：2019-12-02 00:00:00
abstract：:We have used cell-surface-specific labelling techniques and two-dimensional gel electrophoresis to identify proteins on embryonic chick neural retina cells and to determine the effects of Ca2+ on their accessibility to labelling and tryptic removal. A number of proteins on these cells are, in the presence of Ca2+, rel...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1982-06-01 00:00:00
abstract：:MicroRNAs are short non-coding RNAs involved in post-transcriptional regulation of multiple messenger RNA targets. The miR-1/miR-206 family is expressed during skeletal muscle differentiation and is an integral component of myogenesis. To better understand miR-1/miR-206 function during myoblast differentiation we iden...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.101758
更新日期：2012-08-01 00:00:00
abstract：:The identification and characterization of scaffold and targeting proteins of the ERK/MAP kinase pathway is important to understand the function and intracellular organization of this pathway. The F-actin binding protein leukocyte-specific protein 1 (LSP1) binds to PKCbetaI and expression of B-LSP1, an LSP1 truncate c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00955
更新日期：2004-04-15 00:00:00
abstract：:Chromatin is no longer considered to be a static structural framework for packaging DNA within the nucleus but is instead believed to be an interactive component of DNA metabolism. The ordered assembly of chromatin produces a nucleoprotein template capable of epigenetically regulating the expression and maintenance of...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：
更新日期：2000-08-01 00:00:00
abstract：:Clathrin-mediated endocytosis requires cargo-specific adaptor proteins that recognize specific receptors and recruit them into coated pits. ARH [also called low-density lipoprotein receptor (LDLR) adaptor protein] serves as an adaptor for LDLR endocytosis in liver. However, ARH is dispensable for LDL uptake by some ot...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03217
更新日期：2006-10-15 00:00:00
abstract：:MicroRNAs are known to play regulatory roles in gene expression associated with cancer development. We analyzed levels of the microRNA miR-24 in patients with breast carcinoma and found that miR-24 was higher in breast carcinoma samples than in benign breast tissues. We generated constructs expressing miR-24 and studi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.118299
更新日期：2013-03-15 00:00:00
abstract：:Neutrophils enter sites of inflammation by crossing the endothelial lining of the blood vessel wall. VE-cadherin is an endothelial specific, homophilic adhesion molecule located at the lateral cell surface. We have generated a monoclonal antibody against mouse VE-cadherin which inhibits electrical resistance of endoth...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:The degradation of misfolded proteins is essential for cellular homeostasis. Misfolded proteins are normally degraded by the ubiquitin-proteasome system (UPS), and selective autophagy serves as a backup mechanism when the UPS is overloaded. Selective autophagy mediates the degradation of harmful material by its seques...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.214304
更新日期：2018-10-04 00:00:00
abstract：:The metabolism of PI(3,5)P2 is regulated by the PIKfyve, VAC14 and FIG4 complex, mutations in which are associated with hypopigmentation in mice. These pigmentation defects indicate a key, but as yet unexplored, physiological relevance of this complex in the biogenesis of melanosomes. Here, we show that PIKfyve activi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.229500
更新日期：2019-02-28 00:00:00
abstract：:Coronins are conserved F-actin-binding proteins that are important for motility and actin dynamics. Unlike type I coronins, coronin 2A localizes to stress fibers and some focal adhesions, and is excluded from the leading edge. Depletion of coronin 2A in MTLn3 cells decreases cell motility and turnover of focal adhesio...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.051482
更新日期：2009-09-01 00:00:00
abstract：:When oxidative phosphorylation is inhibited in cells of Dictyostelium discoideum, the phosphorylation of tyrosine residues on actin is strongly increased. This increase is fully reversible. Under the same conditions the amoeboid cells undergo a series of shape changes. Within three minutes the pseudopods are withdrawn...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:During the interphase to metaphase transition, microtubules are destabilized by a cdc2 kinase-dependent phosphorylation event. This destabilization is due to a dramatic increase in the rate at which each growing microtubule starts to shrink (catastrophe rate). In principle, this could be brought about by lowering the ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Errors during the first meiotic division are common in our species, but virtually all occur during female meiosis. The reason why oogenesis is more error prone than spermatogenesis remains unknown. Normal segregation of homologous chromosomes at the first meiotic division (MI) requires coordinated behavior of the sist...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-07-01 00:00:00
abstract：:Previously, we showed that an integral component of stored mRNP particles in Xenopus oocytes, Xp54, is a DEAD-box RNA helicase with ATP-dependent RNA-unwinding activity. Xp54 belongs to small family of helicases (DDX6) that associate with mRNA molecules encoding proteins required for progress through meiosis. Here we ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-01-15 00:00:00
abstract：:Brain-derived neurotrophic factor (BDNF) is encoded by multiple mRNA variants whose differential subcellular distribution constitutes a 'spatial code' for local translation of BDNF and selective morphological remodeling of dendrites. Here, we investigated where BDNF translation takes place and what are the signaling p...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.177626
更新日期：2016-07-15 00:00:00
abstract：:T cell activation is accompanied by actin-mediated receptor clustering and reorganization of lipid rafts. It has been suggested that costimulatory molecules might be involved in these processes. We here provide evidence that engagement of the adhesion molecule CD44 initiates cytoskeletal rearrangement and membrane reo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:Melanotransferrin (p97) is an iron-binding membrane glycoprotein with 40% homology to transferrin and lactoferrin. It was first identified on the basis of its high level of expression in melanoma cells, as compared to normal melanocytes. It is also present in many cultured cell types. In normal tissues, p97 is express...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:Rac1 is a small Rho family GTPase that regulates changes in cell morphology associated with cell spreading and migration. Integrin-mediated adhesion is known to activate Rac1 and to regulate the interaction of Rac1 with downstream effectors. Currently, it is not clear how integrins signal Rac1 activation following cel...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00109
更新日期：2002-11-15 00:00:00
abstract：:The path that RNA takes through nuclear pores was mapped using two high-resolution techniques. Unexpectedly, no RNA in HL60 cells was detected by immunogold labelling in the central axis of the pore complex on its way to the transporter at the nuclear membrane; instead, it was distributed around the sides, apparently ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-01-01 00:00:00
abstract：:Efficient trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) to and from the cell surface is essential for maintaining channel density at the plasma membrane (PM) and ensuring proper physiological activity. The most common mutation, F508del, exhibits reduced surface expression and impaired f...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.120196
更新日期：2013-06-15 00:00:00
abstract：:Little is known of the molecular basis for the diversity of microtubule structure and function found within the eukaryotic flagellum. Antibodies that discriminate between tyrosinated alpha tubulin and post-translationally detyrosinated alpha tubulin were used to localize these complementary tubulin isoforms in flagell...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1998-02-01 00:00:00
