1,721,125 research outputs found
The carboxyl terminus of epidermal growth factor receptor/erbB-2 chimerae is internalization impaired
No full textThe endocytosis of gp185erbB-2 was studied using chimeric receptors in which the intracellular domain of erbB-2, or subdomins thereof, was substituted for the corresponding regions of the epidermal growth factor (EGF) receptor. Chimeric and wild-type EGF or erbB-2 receptors were expressed in mouse NIH3T3 or NR6 fibroblasts and in a human mammary adenocarcinoma cell line, MDAMB-134. The rate of EGF-induced internalization for the chimera consisting of the extracellular EGF receptor domain and intracellular erbB-2 domain was reduced three- to fourfold compared with the wild-type EGF receptor. The low rate of internalization of the chimeric receptor resulted in impaired down-regulation and degradation of the receptor. Substitution of the carboxyl terminus of erbB-2 for the corresponding region of the EGF receptor caused a similar decrease of receptor endocytosis, whereas substitution of the erbB-2 tyrosine kinase domain did not affect internalization and down-regulation. Since the tyrosine kinase of the internalization-defective chimeric receptors could be activated by EGF, kinase activity and autophosphorylation of erbB-2 do not appear to be sufficient for a maximum rapid internalization of the chimeric receptors. These results suggest that the carboxyl terminus of erbB-2 either does not possess all the signals required for the rapid internalization or contains an inhibitory signal for rapid internalization
Dynamic characterization of soil and soft rocks of the Central Archeological Area of Rome
No full textThe paper presents the results of in-situ and laboratory tests aimed at defining the
cyclic properties of soils and soft rocks of the Central Archeological Area of Rome in the
framework of the seismic microzonation study of the area. The small-strain shear modulus
G0 (or analogously shear wave velocity VS) and the curves expressing shear modulus G and
damping ratio D variation with shear strain amplitude were investigated. A large amount
of in-hole tests integrated with active surface wave tests were utilized to characterize the
small-strain stiffness of the lithotypes identified in the area. Small-strain stiffness values
determined by geophysical testswere further compared with thosemeasured in the laboratory
showing different behaviors of soils and soft rocks. The effects of sample disturbance and
degree of jointing, for soils and soft rocks, respectively, was invoked to explain the observed
differences. The shear modulus and damping ratio versus shear strain amplitude curves were
determined by means of resonant column and cyclic shear tests, both simple and torsional.
The experimental results were compared with literature data on similar soils highlighting
some peculiar behaviors. In particular the role of fine matrix in sandy soils and organic
matter content of clays on the cyclic properties was stressed. The results showed that an
increase in fine matrix and organic content results in a stronger linearity and lower damping
ratio
Signaling through monoubiquitination
No full textUbiquitination is a post-translational modification in which a small conserved peptide, ubiquitin, is appended to target proteins in the cell, through a series of complex enzymatic reactions. Recently, a particular form of ubiquitination, monoubiquitination, has emerged as a nonproteolytic reversible modification that controls protein function. In this review, we highlight recent findings on monoubiquitination as a signaling-induced modification, controlled, among others, by pathways originating from active receptor tyrosine kinases. Furthermore, we review the major cellular processes controlled by ubiquitin modification, including membrane trafficking, histone function, transcription regulation, DNA repair, and DNA replication
Endocytosis and mitogenic signaling
No full textIs there mitogenic signaling during endocytosis or is receptor internalization mainly an attenuator of signals? Recent data indicate that the answer appears to be yes to both questions. Signal transduction occurs physiologically from the cell surface and endocytosis downregulates signaling by removing receptors from the plasma membrane. In cancer, the involvement of endocytic/sorting proteins points to dysregulation of apparently unrelated pathways, which might account for an important causative role in neoplasia
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The interaction of epsin and Eps15 with the clathrin adaptor AP-2 is inhibited by mitotic phosphorylation and enhanced by stimulation-dependent dephosphorylation in nerve terminals
No full textClathrin-mediated endocytosis was shown to be arrested in mitosis due to a block in the invagination of clathrin-coated pits. A Xenopus mitotic phosphoprotein, MP90, is very similar to an abundant mammalian nerve terminal protein, epsin, which binds the Eps15 homology (EH) domain of Eps15 and the alpha-adaptin subunit of the clathrin adaptor AP-2. We show here that both rat epsin and Eps15 are mitotic phosphoproteins and that their mitotic phosphorylation inhibits binding to the appendage domain of alpha-adaptin. Both epsin and Eps15, like other cytosolic components of the synaptic vesicle endocytic machinery, undergo constitutive phosphorylation and depolarization-dependent dephosphorylation in nerve terminals. Furthermore, their binding to AP-2 in brain extracts is enhanced by dephosphorylation. Epsin together with Eps15 was proposed to assist the clathrin coat in its dynamic rearrangements during the invagination/fission reactions. Their mitotic phosphorylation may be one of the mechanisms by which the invagination of clathrin-coated pits is blocked in mitosis and their stimulation-dependent dephosphorylation at synapses may contribute to the compensatory burst of endocytosis after a secretory stimulus
Direct binding of eps8 to the juxtamembrane domain of EGFR is phosphotyrosine- and SH2-independent
No full textSeveral signal transducers bind through their SH2 domains to phosphotyrosine-containing motifs present in receptor tyrosine kinases (RTKs). However, the juxtamembrane regions of the epidermal growth factor receptor (EGFR) and of the related erbB-2 protein, while important in mitogenic signaling, lack demonstrable tyrosine phosphorylation sites, suggesting that other modalities of receptor-transducer interactions exist. A candidate for investigating this type of association is p97eps8, a recently described substrate for RTKs. p97eps8 is phosphorylated by several RTKs, associates with EGFR in vivo and, upon overexpression, enhances the transduction of EGFR-mediated mitogenic signals. Here we report that eps8 binds directly to the juxtamembrane region of EGFR through a domain that does not bear resemblance to SH2 domains and by a mechanism that does not require the presence of phosphotyrosine residues. Thus, the physical association between EGFR and eps8 represents a novel interaction between RTKs and their substrates
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