scholarly journals Generation of protein kinase Ck1α mutants which discriminate between canonical and non-canonical substrates

2005 ◽  
Vol 391 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Victor H. Bustos ◽  
Oriano Marin ◽  
Flavio Meggio ◽  
Luca Cesaro ◽  
Catherine C. Allende ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Structural Features ◽  
Side Chain ◽  
Cellular Functions ◽  
Peptide Substrates ◽  
Triple Mutation ◽  
Alanine Scan ◽  
Lysine Residues ◽  
The Individual

Protein kinase CK1 denotes a family of pleiotropic serine/threonine protein kinases implicated in a variety of cellular functions. Typically, CK1 acts as a ‘phosphate-directed’ kinase whose targeting is primed by a single phosphorylated side chain at position n−3 or n−4 relative to serine/threonine, but increasing evidence is accumulating that CK1 can also engage some of its substrates at sites that do not conform to this canonical consensus. In the present paper, we show that CK1α phosphorylates with the same efficiency phosphopeptides primed by a phosphoserine residue at either n−3 [pS(−3)] or n−4 [pS(−4)] positions. The phosphorylation efficiency of the pS(−4) peptide, and to a lesser extent that of the pS(−3) peptide, is impaired by the triple mutation of the lysine residues in the K229KQK232 stretch to alanine residues, promoting 40-fold and 6-fold increases of Km respectively. In both cases, the individual mutation of Lys232 is as detrimental as the triple mutation. A kinetic alanine-scan analysis with a series of substituted peptide substrates in which the priming phosphoserine residue was effectively replaced by a cluster of four aspartate residues was also consistent with a crucial role of Lys232 in the recognition of the acidic determinant at position n−4. In sharp contrast, the phosphorylation of β-catenin and of a peptide including the non-canonical β-catenin site (Ser45) lacking acidic/phosphorylated determinants upstream is not significantly affected by mutations in the KKQK stretch. These data provide a molecular insight into the structural features that underlie the site specificity of CK1α and disclose the possibility of developing strategies for the preferential targeting of subsets of CK1 substrates.

The role of the Lewis acid−base properties in the supramolecular association of 1,2,5-chalcogenadiazoles

2013 ◽  
Vol 91 (5) ◽  
pp. 338-347 ◽  
Author(s):  
Anthony F. Cozzolino ◽  
Philip J.W. Elder ◽  
Lucia Myongwon Lee ◽  
Ignacio Vargas-Baca
Keyword(s):  
Topological Analysis ◽  
Structural Features ◽  
Lewis Acidity ◽  
Electron Localization ◽  
Dispersion Forces ◽  
Acid Base ◽  
Lewis Bases ◽  
The Individual ◽  
Secondary Bonding

The secondary bonding interactions that link the supramolecular structures assembled by 1,2,5-chalcogenadiazoles were analyzed through explicit orthogonalization of molecular orbitals (NBO), topological analysis of the electron density (AIM), and the electron localization function (ELF). The results of these analyses are consistent with a bonding description that attributes important covalent and electrostatic character to these interactions. Application of these analyses to the individual molecules highlighted the structural features from which each of those contributions originates, namely the polarity and modest strength of the E–N bond. Both of these effects increase along the series S, Se, Te. Perturbations to the heterocycle electronic structure that result in a weaker and more polar E–N bond cause an increase in the Lewis acidity at the chalcogen centre, which in turn leads to stronger secondary bonding interactions with Lewis bases. Additionally, the contribution of dispersion forces is not negligible and is most important in the case of sulfur.

scholarly journals Protein kinase CK2: structure, regulation and role in cellular decisions of life and death

2003 ◽  
Vol 369 (1) ◽  
pp. 1-15 ◽  
Author(s):  
David W. LITCHFIELD
Keyword(s):  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Serine Threonine Kinase ◽  
Life And Death ◽  
Dual Specificity ◽  
Mechanistic Basis ◽  
Kinase Ck2

Protein kinase CK2 ('casein kinase II') has traditionally been classified as a messenger-independent protein serine/threonine kinase that is typically found in tetrameric complexes consisting of two catalytic (α and/or α′) subunits and two regulatory β subunits. Accumulated biochemical and genetic evidence indicates that CK2 has a vast array of candidate physiological targets and participates in a complex series of cellular functions, including the maintenance of cell viability. This review summarizes current knowledge of the structural and enzymic features of CK2, and discusses advances that challenge traditional views of this enzyme. For example, the recent demonstrations that individual CK2 subunits exist outside tetrameric complexes and that CK2 displays dual-specificity kinase activity raises new prospects for the precise elucidation of its regulation and cellular functions. This review also discusses a number of the mechanisms that contribute to the regulation of CK2 in cells, and will highlight emerging insights into the role of CK2 in cellular decisions of life and death. In this latter respect, recent evidence suggests that CK2 can exert an anti-apoptotic role by protecting regulatory proteins from caspase-mediated degradation. The mechanistic basis of the observation that CK2 is essential for viability may reside in part in this ability to protect cellular proteins from caspase action. Furthermore, this anti-apoptotic function of CK2 may contribute to its ability to participate in transformation and tumorigenesis.

Gossip, Reputation, and Language

2019 ◽  
pp. 81-99
Author(s):  
Haykaz Mangardich ◽  
Stanka A. Fitneva
Keyword(s):  
Experimental Research ◽  
Speech Acts ◽  
Structural Features ◽  
Reputation Management ◽  
Linguistic Features ◽  
Individual Level ◽  
The Public ◽  
Physical Form ◽  
The Individual

Language is deeply involved in the management of human reputations. In this chapter, we review some of the linguistic features that relate to reputation, drawing extensively on ethnographic and experimental research. At the individual level, what the speaker says, and the physical form of speech contribute to establishing the public face of the speaker. At the interaction level, linguistic devices such as hedges and silences regulate the relations among speakers, expressing politeness, deference, acceptance, or rejection. Finally, linguistic speech acts such as apologies explicitly manipulate the speaker’s and others’ reputations. We also highlight some of the structural features of gossip, which is a genre of conversation that paradigmatically illustrates the role of language in reputation management.

scholarly journals Role of the htrA Gene in Klebsiella pneumoniae Virulence

2002 ◽  
Vol 70 (9) ◽  
pp. 4772-4776 ◽  
Author(s):  
Guadalupe Cortés ◽  
Beatriz de Astorza ◽  
Vicente J. Benedí ◽  
Sebastián Albertí
Keyword(s):  
Klebsiella Pneumoniae ◽  
Parent Strain ◽  
Structural Features ◽  
Side Chain ◽  
Mice Model ◽  
Complement Component C3 ◽  
Human Sera ◽  
And Oxidative Stress

ABSTRACT We recently described the use of mini-Tn5 to generate complement-sensitive mutants derived from a complement-resistant Klebsiella pneumoniae clinical isolate deficient in the lipopolysaccharide O side chain. One mutant with a reduced capacity to survive in nonimmune human sera carried the transposon inserted in the htrA gene. We cloned and sequenced the gene and predicted from the deduced amino acid sequence that the putative HtrA homolog contains structural features similar to those of previously described HtrA proteins. To investigate the biological functions and the role of the htrA gene in the virulence of K. pneumoniae, we constructed an isogenic mutant by insertion-duplication mutagenesis. Characterization of the mutant showed that it had greater sensitivity to temperature (50°C) and oxidative stress (H2O2) than the parent strain. Furthermore, the htrA mutant produced less capsule, bound more molecules of complement component C3, and was more sensitive to complement and whole-blood killing than was the parent strain. Finally, disruption of the htrA gene in a virulent K. pneumoniae strain caused a reduction of its virulence in a mice model. Our results indicate that the htrA gene plays an important role in the virulence of K. pneumoniae.

scholarly journals Aurora-A site specificity: a study with synthetic peptide substrates

2005 ◽  
Vol 390 (1) ◽  
pp. 293-302 ◽  
Author(s):  
Stefano Ferrari ◽  
Oriano Marin ◽  
Mario A. Pagano ◽  
Flavio Meggio ◽  
Daniel Hess ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Structural Features ◽  
Aurora A ◽  
Hydrophobic Residue ◽  
Peptide Substrates ◽  
Mechanism Of Reaction ◽  
A Site ◽  
Derivatives Of ◽  
Autophosphorylation Site

AurA (Aurora-A) is a ubiquitous protein kinase regulating entry into mitosis and shown to promote transformation upon overexpression. In order to gain information on the structural features determining its substrate specificity, we assayed human recombinant AurA on a variety of phosphoacceptor peptide substrates including a series of properly modified derivatives of the Kemptide (ALRRASLGAA). The data presented here show that AurA is a basophilic Ser/Thr protein kinase recognizing the consensus R/K/N-R-X-S/T-B, where B denotes any hydrophobic residue with the exception of Pro. We show that the presence of a Pro at position n+1 fully abrogates phosphorylation of the peptide substrate. Although the consensus for AurA is reminiscent of that of PKA (protein kinase A), it significantly differs from the latter for a much more stringent dependence on the hydrophobic residue at n+1 and for its tolerance of residues other than Arg at position n−3. Based on the finding that the peptide ALKRASLGAA is not a substrate of PKA while still providing a sensitive assay of AurA activity, we suggest that this peptide may be used for differential screening of the two kinases. We have further validated the AurA consensus by generating a peptide (APSSRRTT288LCGT) that comprises the main AurA autophosphorylation site and by showing that AurA phosphorylated this peptide exclusively at one site fulfilling its consensus (Thr288). Moreover, we show that AurA could autophosphorylate at Thr288 through an intermolecular mechanism of reaction and that, in vivo, PKA was not involved with Thr288 phosphorylation. The evidence obtained in the present study provides a rational tool for predicting AurA sites in potential substrates of physiological significance.

scholarly journals New Insights into Cellular Functions of Nuclear Actin

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 304
Author(s):  
Malgorzata Kloc ◽  
Priyanka Chanana ◽  
Nicole Vaughn ◽  
Ahmed Uosef ◽  
Jacek Z. Kubiak ◽  
...  
Keyword(s):  
Cell Fate ◽  
Analytical Techniques ◽  
Nuclear Actin ◽  
Epigenetic Landscape ◽  
Cellular Functions ◽  
Organ Differentiation ◽  
Cytoplasmic Actin ◽  
The Individual ◽  
Commercial Antibodies

Actin is one of the most abundant proteins in eukaryotic cells. There are different pools of nuclear actin often undetectable by conventional staining and commercial antibodies used to identify cytoplasmic actin. With the development of more sophisticated imaging and analytical techniques, it became clear that nuclear actin plays a crucial role in shaping the chromatin, genomic, and epigenetic landscape, transcriptional regulation, and DNA repair. This multifaceted role of nuclear actin is not only important for the function of the individual cell but also for the establishment of cell fate, and tissue and organ differentiation during development. Moreover, the changes in the nuclear, chromatin, and genomic architecture are preamble to various diseases. Here, we discuss some of the newly described functions of nuclear actin.

scholarly journals The role of the phosphate group for the structure of phosphopeptide products of adenosine 3',5'-cyclic monophosphate-dependent protein kinase

1985 ◽  
Vol 229 (2) ◽  
pp. 485-489 ◽  
Author(s):  
R C Hider ◽  
U Ragnarsson ◽  
O Zetterqvist
Keyword(s):  
Structural Change ◽  
Protein Kinase ◽  
Aqueous Media ◽  
Dependent Protein Kinase ◽  
High Tendency ◽  
Peptide Substrates ◽  
Random Structures ◽  
Dependent Protein ◽  
Guanidinium Salt

By c.d. studies it is shown that liver-pyruvate-kinase-related peptide substrates of cyclic AMP-dependent protein kinase have a high tendency towards non-random structures in non-aqueous media. When phosphorylated, the conformation tendencies decrease. This structural change is explained in terms of the formation of strong intrapeptide phosphate-guanidinium salt links. It is proposed that similar events occur at the catalytic site of protein kinase and that such an interaction could facilitate the removal of the phosphorylated products.

scholarly journals Role of protein kinase C isozymes in cellular functions and pathological conditions.

2002 ◽  
Vol 119 (2) ◽  
pp. 65-78 ◽  
Author(s):  
Tetsuhiro HISAYAMA ◽  
Koichi NAKAYAMA ◽  
Naoaki SAITO ◽  
Yasuki KIHARA ◽  
Shigeru NISHIZAWA ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cellular Functions ◽  
Kinase C ◽  
Pathological Conditions

scholarly journals The Interpretive Shaping of Music Performance Research

2013 ◽  
Vol 8 (2) ◽  
pp. 120 ◽  
Author(s):  
John Rink
Keyword(s):  
Empirical Research ◽  
Music Performance ◽  
Structural Features ◽  
Musical Performance ◽  
The Individual ◽  
Music Performance Research ◽  
Performance Research ◽  
Shed Light

<p>In their study of nine pianists Buck, MacRitchie and Bailey observe a universal embodiment of phrasing structure and other higher-level structural features of the music, the physical makeup of which is nevertheless particular to both the individual performers and the pieces they are performing. Such a conclusion invites renewed consideration of assumptions in the literature on musical performance about the nature and role of structure and about performers&rsquo; &lsquo;interpretations&rsquo; thereof. The findings also raise interesting questions about the musical viability of empirical research on performance and its capacity to shed light on how performers shape the music they play, their motivations in doing so, and how those listening to them might in turn be affected by this.</p>

scholarly journals Role of Ca2+/ca Imodu1in-dependent protein kinase II in cellular functions of adrenal medulla

1995 ◽  
Vol 67 ◽  
pp. 77
Author(s):  
Hobuyuki Yanagihara ◽  
Masato Tsutsui ◽  
Yumiko Toyohira ◽  
Kouichiro Minami ◽  
Susmu Ueno ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Adrenal Medulla ◽  
Cellular Functions ◽  
Dependent Protein Kinase ◽  
Protein Kinase Ii ◽  
Dependent Protein
Sign in / Sign up

Export Citation Format

Share Document