Abstract：
:Various agents are able to stimulate the EGF receptor protein tyrosine kinase in the absence of ligand binding. To characterize their mechanism of action, we investigated their effects on the kinase activity of the intracellular domain of the EGF receptor (EGFR-IC). EGFR-IC (67 kDa) lacking the extracellular domain and transmembrane segment of the EGF receptor, but retaining kinase and autophosphorylation domains, was produced and purified as a soluble, cytoplasmic protein from Sf9 insect cells infected with a recombinant baculovirus. EGFR-IC was able to undergo autophosphorylation in a manner similar to full-length EGFR. Synthetic substrate peptides showed similar affinity to EGFR-IC as to the full-length receptor. The activity of the EGFR-IC was found to be dependent on divalent cations, Mn2+ being a more potent activator than Mg2+. Agents capable of aggregating the kinase by direct interaction (cross-linking antibodies, polycations) or through altering the surrounding solvent structure and thereby decreasing protein solubility [ammonium sulfate, poly(ethylene glycol), 2-methyl-2,4-pentanediol] activated the kinase in a manner which correlated with their ability to precipitate the EGFR intracellular domain. The widely different chemical nature of these agents suggests that they do not act by direct interaction with specific allosteric regulatory sites, but rather by facilitating the interactions between kinase molecules. These results support the hypothesis that full-length receptor aggregation itself, induced by ligand binding to the extracellular domain, results in intracellular domain interactions and the activation of kinase activity.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Mohammadi M,Honegger A,Sorokin A,Ullrich A,Schlessinger J,Hurwitz DRdoi
10.1021/bi00085a004subject
Has Abstractpub_date
1993-08-31 00:00:00pages
8742-8issue
34eissn
0006-2960issn
1520-4995journal_volume
32pub_type
杂志文章相关文献
BIOCHEMISTRY文献大全abstract：:alpha5beta1 integrin can occupy several distinct conformational states which support different strengths of binding to fibronectin [García, A. J., et al. (1998) J. Biol. Chem. 273, 34710-34715]. Using a model system in which specific activating monoclonal antibodies were used to achieve uniform activated states, the b...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi025752f
更新日期：2002-07-23 00:00:00
abstract：:A new procedure to cleave tryptophanyl peptide bonds in high yield is reported. The method involves treatment of the S-alkylated protein with o-iodosobenzoic acid. The procedure is highly selective for tryptophan and does not modify tyrosine or histidine, but may convert methionine to its sulfoxide derivative. The yie...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00584a026
更新日期：1979-08-21 00:00:00
abstract：:Fusion of the human immunodeficiency virus (HIV) with target cells is mediated by the gp41 subunit of the envelope protein. Mutation and deletion studies within the transmembrane domain (TMD) of intact gp41 influenced its fusion activity. In addition, current models suggest that the TMD is in proximity with the fusion...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi201721r
更新日期：2012-04-03 00:00:00
abstract：:The p90 ribosomal S6 family of kinases (RSK) are potential drug targets, due to their involvement in cancer and other pathologies. There are currently only two known selective inhibitors of RSK, but the basis for selectivity is not known. One of these inhibitors is a naturally occurring kaempferol-α-L-diacetylrhamnosi...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi300620c
更新日期：2012-08-21 00:00:00
abstract：:Six rhodopsin mutants containing disulfide cross-links between different cytoplasmic regions were prepared: disulfide bond 1, between Cys65 (interhelical loop I-II) and Cys316 (end of helix VII); disulfide bond 2, between Cys246 (end of helix VI) and Cys312 (end of helix VII); disulfide bond 3, between Cys139 (end of ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9912443
更新日期：1999-09-28 00:00:00
abstract：:The oxygen enzymatically inserted as a hydroxyl function by chick kidney homogenate into the 24 position of 25-hydroxyvitamin D3 to give 24,25-dihydroxyvitamin D3 is derived exclusively from 18O2. Therefore, like the 25-hydroxyvitamin D3-lalpha-hydroxylase system, the 25-hydroxyvitamin D3-24-hydroxylase system is also...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00629a015
更新日期：1977-05-17 00:00:00
abstract：:Plexins are transmembrane proteins that serve as guidance receptors during angiogenesis, lymphangiogenesis, neuronal development, and zebrafish fin regeneration, with a putative role in cancer metastasis. Receptor dimerization or clustering, induced by extracellular ligand binding but modulated in part by the plexin t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.6b00517
更新日期：2016-09-06 00:00:00
abstract：:The paramagnetic enhancements in the NMR relaxation rates for the fluorine in fluorophthalates have been used to determine the position of the phthalate with respect to the mononuclear metal ion in native and metal-substituted derivatives of phthalate dioxygenase (PDO). These studies show directly that the substrate i...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi990431y
更新日期：1999-08-24 00:00:00
abstract：:Haemadin is a 57-amino acid thrombin inhibitor from the land-living leech Haemadipsa sylvestris, whose structure has recently been determined in complex with human alpha-thrombin. Here we communicate the effect of ionic strength on the kinetics of the inhibition of human alpha-thrombin by haemadin, by using thrombin m...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi011605q
更新日期：2002-02-26 00:00:00
abstract：:A newly reported strain of Vibrio cholerae, known as strain O139 Bengal, is the first instance of an encapsulated strain that has caused epidemic cholera. The O-antigenic capsule is the critical antigen for protective immunity. Since mapping of the antigenic epitopes will assist in the development of a protein conjuga...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi9910272
更新日期：1999-09-14 00:00:00
abstract：:Quasi-elastic laser light scattering is used to examine the cholera toxin mediated agglutination of ganglioside GM1 containing phospholipid vesicles and Gm1-coated polystyrene spheres. We find that the ability of cholera toxin to agglutinate Gm1-containing phospholipid vesicles depends markedly on the lipid compositio...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00256a031
更新日期：1982-06-22 00:00:00
abstract：:The kinetic and thermodynamic features of reactions catalyzed by present-day enzymes appear to be the consequence of the evolution of these proteins toward maximal catalytic effectiveness. These features are identified and analyzed (in detail for one substrate-one product enzymes) by using ideas that link the energeti...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00450a009
更新日期：1989-11-28 00:00:00
abstract：:Heme oxygenase (HO) catalyzes the regiospecific cleavage of the porphyrin ring of heme using reducing equivalents and O2 to produce biliverdin, iron, and CO. Because CO has a cytoprotective effect through the p38-MAPK pathway, HO is a potential therapeutic target in cancer. In fact, inhibition of the HO isoform HO-1 r...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi062264p
更新日期：2007-02-20 00:00:00
abstract：:In prokaryotes, a large share of the proteins are secreted from the cell through a process that requires their translocation across the cytoplasmic membrane. This process is mediated by the universally conserved Sec system with homologues in the endoplasmic reticulum and thylakoid membranes of eukaryotes. The Sec syst...
journal_title：Biochemistry
pub_type： 杂志文章,评审
doi：10.1021/bi400913x
更新日期：2013-10-01 00:00:00
abstract：:A study of the dynamics and mechanism of the various thermotropic phase transitions undergone by the hydrated monoacylglycerides monoolein and monoelaidin, in the temperature range of 20-120 degrees C and from 0 to 5 M NaCl, has been undertaken. Measurements were made by using time-resolved X-ray diffraction at the Co...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00394a008
更新日期：1987-10-06 00:00:00
abstract：:Proteins denature at low pH because of intramolecular electrostatic repulsions. The addition of salt partially overcomes this repulsion for some proteins, yielding a collapsed conformation called the A-state. A-states have characteristics expected for the molten globule, a notional kinetic protein folding intermediate...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi981364v
更新日期：1998-12-01 00:00:00
abstract：:The data and approach reported in paper I (Hanlon et al., 1975, preceding paper) have been used to calculate the fractional changes in secondary structure of calf thymus deoxyribonucleic acid which occur in aqueous solutions as a function of the concentration of NaCl, KCl, LiCl, CsCl, and NH4Cl. There is a continuous ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00679a018
更新日期：1975-04-22 00:00:00
abstract：:We report the genetically encoded chemical decaging strategy for protein activation in living bacterial cells. In contrast to the metabolically labile photocaging groups inside Escherichia coli, our chemical decaging strategy that relies on the inverse electron-demand Diels-Alder (iDA) reaction is compatible with the ...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.7b01017
更新日期：2018-01-30 00:00:00
abstract：:The secondary structure of protein kinase C alpha (PKC alpha) has been studied using infrared spectroscopy in the presence of both H(2)O and D(2)O buffers. In the absence of ligands at 20 degrees C, it was shown that beta-sheet is the major component, representing about 44% of the total structure, whereas the alpha-he...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi035128i
更新日期：2004-03-02 00:00:00
abstract：:Binding of streptokinase (SK) to plasminogen (Pg) activates the zymogen conformationally and initiates its conversion into the fibrinolytic proteinase, plasmin (Pm). Equilibrium binding studies of SK interactions with a homologous series of catalytic site-labeled fluorescent Pg and Pm analogues were performed to resol...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi000594i
更新日期：2000-11-14 00:00:00
abstract：:Integrin conformational changes mediate integrin activation and signaling triggered by intracellular molecules or extracellular ligands. Even though it is known that αβ transmembrane domain separation is required for integrin signaling, it is still not clear how this signal is transmitted from the transmembrane domain...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi101462h
更新日期：2010-11-30 00:00:00
abstract：:Human protein Z is a vitamin K-dependent plasma glycoprotein, deficiency of which leads to a mild bleeding tendency. Protein Z appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. In this study, to characterize the gene for protein Z, its organization and structure...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi972002a
更新日期：1998-05-12 00:00:00
abstract：:Assembly of the type I procollagen molecule begins with interactions among the C-pro alpha1(I) and C-pro alpha2(I) domains. The C-propeptide domains themselves have subdomains of distinct structures. The important questions are where chain association begins and the basis of the chain selectivity which leads to the pr...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0508338
更新日期：2005-11-22 00:00:00
abstract：:It now appears that photosynthetic prokaryotes and lower eukaryotes possess higher plant phytochrome-like proteins. In this work, a second phytochrome-like gene was isolated, in addition to the recently identified Cph1 phytochrome, from the Synechocystis sp. PCC 6803, and its gene product was characterized photochemic...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi992831r
更新日期：2000-09-05 00:00:00
abstract：:Trinucleotide repeat expansion diseases (TREDs) are correlated with elongation of CNG DNA and RNA repeats to pathological level. This paper shows, for the first time, complete data concerning thermodynamic stabilities of RNA with CNG trinucleotide repeats. Our studies include the stability of oligoribonucleotides comp...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0502339
更新日期：2005-08-16 00:00:00
abstract：:Members of the ATP-binding cassette (ABC) transporters share the same basic architecture, with a four-core domain made of two transmembrane plus two nucleotide-binding domains. However, a supramolecular organization has been detected in some ABC transporters, which might be relevant to physiological regulation of subs...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi0482809
更新日期：2005-03-22 00:00:00
abstract：:Molecular chaperones facilitate the folding and assembly of proteins and inhibit their aberrant aggregation. They thus offer several opportunities for biomedical and biotechnological applications, as for example they can often prevent protein aggregation more effectively than other therapeutic molecules, including sma...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.5b00459
更新日期：2015-08-18 00:00:00
abstract：:DNA photolyases catalyze the splitting of the cyclobutane ring joining the two dihydropyrimidines of a pyrimidine dimer by a photoinduced electron-transfer reaction. Previous studies concluded that photolyase repairs only the cis-syn form of the eight stereoisomers of the cyclobutane pyrimidine dimer (Pyr[ ]Pyr). In t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00079a001
更新日期：1993-07-20 00:00:00
abstract：:Intrastrand cross-links (IaCL) connecting two purine nucleobases in DNA pose a challenge to high-fidelity replication in the cell. Various repair pathways or polymerase bypass can cope with these lesions. The influence of the phosphodiester linkage between two neighboring 2'-deoxyguanosine (dG) residues attached throu...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/acs.biochem.5b01078
更新日期：2015-12-29 00:00:00
abstract：:Chemical modification of Torpedo californica acetylcholinesterase by various sulfhydryl reagents results in its conversion to one of two principal states. One of these states, viz., that produced by disulfides and alkylating agents, is stable. The second state, produced by mercury derivatives, is metastable. At room t...
journal_title：Biochemistry
pub_type： 杂志文章
doi：10.1021/bi00252a006
更新日期：1994-12-06 00:00:00
