Abstract:
:Fibroblast growth factor (FGF) receptor substrate 2 (FRS2) is a membrane-anchored docking protein that has been shown to play an important role in linking FGF, nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF) receptors with the Ras/mitogen-activated protein (MAP) kinase signaling cascade. Here we provide evidence that FRS2 can also play a role in epidermal growth factor (EGF) signaling. Upon EGF stimulation, FRS2 mediates enhanced MAPK activity and undergoes phosphorylation on tyrosine as well as serine/threonine residues. This involves the direct interaction of the FRS2 PTB domain with the EGFR and results in a significantly altered mobility of FRS2 in SDS-PAGE which is also observed in FGF stimulated cells. This migration shift of FRS2 is completely abrogated by U0126, a specific MAPK kinase 1 (MEK1) inhibitor, suggesting that ERK1/2 acts as serine/threonine kinase upstream of FRS2. Indeed, we show that the central portion of FRS2 constitutively associates with ERK1/2, whereas the FRS2 carboxy-terminal region serves as substrate for ERK2 phosphorylation in response to EGF and FGF stimulation. Notably, tyrosine phosphorylation of FRS2 is enhanced when ERK1/2 activation is inhibited after both EGF and FGF stimulation. These results indicate a ligand-stimulated negative regulatory feedback loop in which activated ERK1/2 phosphorylates FRS2 on serine/threonine residues thereby down-regulating its tyrosine phosphorylation. Our findings support a broader role of FRS2 in EGFR-controlled signaling pathways in A-431 cells and provide insight into a molecular mechanism for ligand-stimulated feedback regulation with FRS2 as a central regulatory switch point.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Wu Y,Chen Z,Ullrich Adoi
10.1515/BC.2003.134keywords:
subject
Has Abstractpub_date
2003-08-01 00:00:00pages
1215-26issue
8eissn
1431-6730issn
1437-4315journal_volume
384pub_type
杂志文章abstract::Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 1...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2008.085
更新日期:2008-06-01 00:00:00
abstract::Molecular chaperones of the heat shock protein 70 (Hsp70) family play a crucial role in the presentation of exogenous antigenic peptides by antigen-presenting cells (APCs). In a combined biochemical and immunological approach, we characterize the biochemical interaction of tumor-associated peptides with human Hsp70 an...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2009.038
更新日期:2009-04-01 00:00:00
abstract::The saline extract of Bauhinia bauhinioides dry seeds was shown to inhibit cruzipain, a cysteine proteinase from Trypanosoma cruzi. The inhibitory activity was assigned to a protein with 164 amino acid residues and molecular mass of 18 034 Da that was purified by chromatography on DEAE-Sephadex, trypsin-Sepharose (rem...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2001.103
更新日期:2001-05-01 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV8) is a gammaherpesvirus and the etiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman disease. The KSHV genome contains genes for a unique group of proteins with homology to cellular interferon regulatory ...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2017-0111
更新日期:2017-07-26 00:00:00
abstract::Angiotensin-converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis, and several aspects of the immune response. ACE 10/10 mice overexpress ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization t...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2013-0295
更新日期:2014-10-01 00:00:00
abstract::Reactive oxygen and nitrogen species deposited by cold physical plasma are proposed as predominant effectors in the interaction between discharge and biomedical application. Most reactive species found in plasma sources are known in biology for inter- and intracellular communication (redox signaling) and mammalian cel...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2018-0242
更新日期:2018-12-19 00:00:00
abstract::Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxid...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2008.033
更新日期:2008-03-01 00:00:00
abstract::Recombinant expression of actin in bacteria results in non-native species that aggregate into inclusion bodies. Actin is a folding substrate of TRiC, the chaperonin of the eukaryotic cytosol. By employing bacterial in vitro translation lysates supplemented with purified chaperones, we have found that TRiC is the only ...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2005.088
更新日期:2005-08-01 00:00:00
abstract::Protein transport, especially into different cellular compartments, is a highly coordinated and regulated process. The molecular machineries which carry out these transport processes are highly complex in structure, function, and regulation. In the case of chloroplasts, thousands of protein molecules have been estimat...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2009.051
更新日期:2009-08-01 00:00:00
abstract::Ammonia is a major player in the pathogenesis of hepatic encephalopathy (HE) and affects astrocyte function by triggering a self-amplifying cycle between osmotic and oxidative stress. We recently demonstrated that hypoosmotic astrocyte swelling rapidly stimulates nitric oxide (NO) production and increases intracellula...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2011.199
更新日期:2011-12-01 00:00:00
abstract::Bradykinin (BK) is a vasorelaxant, algesic and inflammatory agent. Angiotensin II (AngII) is known to control vascular tone and promote growth, inflammation and artherogenesis. There is evidence for cross talking between BK and AngII receptors. Therefore, the effect of lack of kinin receptors was assessed in mice with...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2009.081
更新日期:2009-09-01 00:00:00
abstract::Interleukin-13 (IL-13) is a T-cell-derived pleiotropic cytokine of particular medical importance because of its critical role in the development of allergic asthma. The effects of IL-13 on its target cells are mediated through a dimeric transmembrane receptor (IL-13R), which shares the IL-4Ralpha subunit with the IL-4...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2007.036
更新日期:2007-03-01 00:00:00
abstract::Here we report a detailed analysis of magnesium (Mg²+) ion effects on furin hydrolysis of fluorescent resonance energy transfer decapeptide substrates derived from canonical R-X-K/R-R furin cleavage motifs within certain viral envelope glycoproteins and eukaryotic proproteins. Using virus-derived sequences a selective...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2010.114
更新日期:2010-09-01 00:00:00
abstract::Recent progress in the identification and partial characterization of novel genes encoding cysteine proteases of the papain family has considerably increased our knowledge of this family of enzymes. Kinetic data available to date for this large family indicate relatively broad, overlapping specificities for most enzym...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2003.094
更新日期:2003-06-01 00:00:00
abstract::To elucidate the structures and dynamics of membrane proteins, highly advanced biophysical methods have been developed that often require significant resources, both for sample preparation and experimental analyses. For very complex systems, such as membrane transporters, ion channels or G-protein coupled receptors (G...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/hsz-2018-0473
更新日期:2019-09-25 00:00:00
abstract::Nanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment due to their targeted drug release. Gastric cancer is an important killer disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microsc...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2017-0208
更新日期:2018-02-23 00:00:00
abstract::G-protein coupled receptor 119 (GPR119) is emerging as a potential target for the treatment of type 2 diabetes with beneficial effects on glucose homeostasis. This study assessed the insulin-secreting properties of various GPR119 agonists and the distribution of GPR119 in pancreatic islets. Endogenous ligands [oleoyle...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2013-0255
更新日期:2014-04-01 00:00:00
abstract::Group II introns are autocatalytic RNAs which self-splice in vitro. However, in vivo additional protein factors might be involved in the splicing process. We used an affinity chromatography method called 'StreptoTag' to identify group II intron binding proteins from Saccharomyces cerevisiae. This method uses a hybrid ...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2004.076
更新日期:2004-07-01 00:00:00
abstract::As an important protein, UL31 has been demonstrated to play multiple roles in herpes simplex virus 1 (HSV-1) replication. Previous studies showed that UL31 predominantly locates in the nucleus in chemical fixed cells and live cells, however, the determining mechanisms for its nuclear translocation is not clear. In the...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/hsz-2015-0299
更新日期:2016-06-01 00:00:00
abstract::Characterization of protein damage during photosensitization of chlorin e6-treated cells was performed using the green fluorescent protein (GFP). The GFP-chromophore damage caused by singlet oxygen was studied in COS 7 kidney cells and E. coli bacteria following light irradiation. Electron spin resonance (ESR) reveale...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2000.153
更新日期:2000-12-01 00:00:00
abstract::The average amount of cholesterol in the whole animal equals approximately 2100 mg/kg body weight, and 15% and 23% of this sterol in the mouse and human, respectively, is found in the central nervous system. There is no detectable uptake across the blood-brain barrier of cholesterol carried in lipoproteins in the plas...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2009.035
更新日期:2009-04-01 00:00:00
abstract::We have studied ribonuclease T1 (EC 3.1-27.3)-catalysed synthesis of guanylyl-(3'-->5')cytidine in frozen aqueous reaction mixtures at -10 degrees C and in solution at 0 degree C in order to investigate whether ribonuclease-catalysed synthetic reactions can take advantage of the yield-increasing effect of freezing as ...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/bchm.1997.378.2.115
更新日期:1997-02-01 00:00:00
abstract::Here, we describe a novel member in the group of membrane-anchored chymotrypsin (S1)-like serine proteases, namely testis serine protease 1 (T-SP1), as it is principally expressed in testis tissue. The human T-SP1 gene encompasses 28.7 kb on the short arm of chromosome 8 and consists of seven exons. Rapid amplificatio...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2008.170
更新日期:2008-12-01 00:00:00
abstract::Cathepsin E (CE) is an intracellular aspartic proteinase implicated in various physiological and pathological processes, yet its actual roles in vivo remain elusive. To assess the physiological significance of CE expression in tumor cells, human CE was stably expressed in human prostate carcinoma ALVA101 cells express...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2007.154
更新日期:2007-11-01 00:00:00
abstract::Functional ribonuclease A was presented on the surface of the filamentous phage M13 by fusion to the minor coat protein. RNase activity of the fusion protein was shown by a zymogram assay. In addition, we established a modified method for preparing RNase-displaying phages without contaminating host RNases. ...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2000.024
更新日期:2000-02-01 00:00:00
abstract::The lysosomal lumen contains numerous acidic hydrolases involved in the degradation of carbohydrates, lipids, proteins, and nucleic acids, which are basic cell components that turn over continuously within the cell and/or are ingested from outside of the cell. Deficiency in almost any of these hydrolases causes accumu...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2006.135
更新日期:2006-08-01 00:00:00
abstract::One of the control mechanisms of cathepsin B biosynthesis and trafficking operates through alternative splicing of pre-mRNA. An mRNA lacking exon 2 is more efficiently translated than that containing all exons, and may be responsible for elevated biosynthesis and enzyme routing to the extracellular space, with critica...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:10.1515/BC.2006.125
更新日期:2006-08-01 00:00:00
abstract::The lysosomal cysteine proteinase cathepsin B has been implicated in the progression of various human tumors including ovarian cancer. Included in this study were 63 patients with epithelial ovarian carcinoma. Follow-up information (median follow-up period 7 years) was available for all patients, among whom 42 (66.7%)...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2002.146
更新日期:2002-07-01 00:00:00
abstract::The cloning of a Ca2+(0)-sensing receptor (CaR) from parathyroid and kidney, coupled with the identification of inherited disorders in Ca2+(0)-sensing resulting from inactivating or activating mutations of this CaR, has provided substantial insights into how Ca2+(0) is regulated at a systemic level. The CaR plays a ce...
journal_title:Biological chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1997-08-01 00:00:00
abstract::Two current hypotheses of O2 sensing in the carotid body (CB) chemoreceptors suggest participation of oxygen reactive (ROS) species, but they are mechanistically opposed. One postulates that hypoxia decreases ROS levels; the other that hypoxia increases them. Yet, both propose that the ensuing alteration in the cellul...
journal_title:Biological chemistry
pub_type: 杂志文章
doi:10.1515/BC.2004.021
更新日期:2004-03-01 00:00:00