1,721,037 research outputs found
Role of post-translational modifications on cell distribution and FUNCTIONS of protein kinase C theta
No full textThe novel protein kinase C (PKC) theta isozyme has been recently proposed as a drug target
for human leukemias. In single cell types we have identified multiple PKC theta forms,
characterised by differential post-translational modifications. Aim of this work was to
establish if these molecular modifications affect PKC theta intracellular localisation and
catalytic competence.
A critical role in the control of both PKC theta cell distribution and catalytic activity is played
by the phosphorylation state of the kinase activation loop, at the Thr538 residue. PKC theta
molecules showing a Mr of 85 kDa (named theta-85) and dephosphorylated at Thr538 have
been found specifically associated with the Golgi complex and catalytically active. In
contrast, PKC theta molecules with a Mr of 76 kDa (named theta-76), partially
phosphorylated at Thr538, are localised in the detergent-soluble cell fraction. Only theta-76
kinase forms not phosphorylated at Thr538 can undergo conversion to theta-85 by an
autophosphorylation process. Cell treatment with calyculin A, a protein phosphatase 1 and 2A
inhibitor or with LY294002, an inhibitor of Thr538 phosphorylation via PI3K/PDK1, results in
a significant increase in the amount of protein kinase PKC theta associated with the Golgi
complex. Moreover, as demonstrated by the behaviour of Thr538ÆAla and Thr538 ÆGlu PKC
theta mutants, the absence of pThr538 is sufficient for the recruitment of PKC theta to the
Golgi complex. Moreover, the Thr538ÆAla PKC theta mutant also results modified by Nglycosylation.
This kinase form binds wheat germ agglutinin and acquires a lower Mr by
treatment with N-glycosydase F. These findings suggest that different PKC theta forms might
be involved in distinct cell functions. New pharmacological strategies, aimed specifically to
control PKC theta activities that promote malignant cell proliferation, should be designed and
screened on the basis of their effect on individual PKC theta forms
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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Functional role of the charge at the T538 residue in the control of protein kinase C theta
No full textWe show that protein kinase C (PKC) h localized at the Golgi complex is partially conjugated to monoubiquitin. Using the inactive T538A and activable T538E mutants of PKCh, we demonstrate that the presence of an uncharged residue at the 538 position of the activation loop favors both association with the
Golgi and monoubiquitination of the kinase. Moreover, the inactive PKCh does not translocate from the
Golgi in response to a short-term cell stimulation with a phorbol ester and is subjected to different proteolytic degradation pathways compared to the activable cytosolic kinase. These findings highlight the
role of T538 as a critical determinant to address the activable and the inactive PKCh molecules to different
intracellular compartments and to specific post-transductional modifications. The functional relevance of
these observations is supported by the impaired cell division observed in phenotypes expressing high
levels of the inactive PKCh.
2008 Elsevier Inc. All rights reserved
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