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- Andersen, T. C. B., et al.
(författare)
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The SH3 domains of the protein kinases ITK and LCK compete for adjacent sites on T cell?specific adapter protein
- 2019
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 294:42, s. 15480-15494
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Tidskriftsartikel (refereegranskat)abstract
- T-cell activation requires stimulation of specific intracellular signaling pathways in which protein-tyrosine kinases, phosphatases, and adapter proteins interact to transmit signals from the T-cell receptor to the nucleus. Interactions of LCK proto-oncogene, SRC family tyrosine kinase (LCK), and the IL-2?inducible T cell kinase (ITK) with the T cell-specific adapter protein (TSAD) promotes LCK-mediated phosphorylation and thereby ITK activation. Both ITK and LCK interact with TSAD's proline-rich region (PRR) through their Src homology 3 (SH3) domains. Whereas LCK may also interact with TSAD through its SH2 domain, ITK interacts with TSAD only through its SH3 domain. To begin to understand on a molecular level how the LCK SH3 and ITK SH3 domains interact with TSAD in human HEK293T cells, here we combined biochemical analyses with NMR spectroscopy. We found that the ITK and LCK SH3 domains potentially have adjacent and overlapping binding sites within the TSAD PRR amino acids (aa) 239?274. Pulldown experiments and NMR spectroscopy revealed that both domains may bind to TSAD aa 239?256 and aa 257?274. Co-immunoprecipitation experiments further revealed that both domains may also bind simultaneously to TSAD aa 242?268. Accordingly, NMR spectroscopy indicated that the SH3 domains may compete for these two adjacent binding sites. We propose that once the associations of ITK and LCK with TSAD promote the ITK and LCK interaction, the interactions among TSAD, ITK, and LCK are dynamically altered by ITK phosphorylation status.
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| 3. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Equivalence between spectral properties of graphs with and without loops
- 2018
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper we introduce a spectra preserving relation between graphs with loops and graphs without loops. This relation is achieved in two steps. First, by generalizing spectra results got on (m, k)-stars to a wider class of graphs, the (m, k, s)-stars with or without loops. Second, by defining a covering space of graphs with loops that allows to remove the presence of loops by increasing the graph dimension. The equivalence of the two class of graphs allows to study graph with loops as simple graph without loosing information.
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| 4. |
- Andreotti, Eleonora, 1988, et al.
(författare)
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Measuring stability of spectral clustering
- 2019
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Ingår i: Linear Algebra and Its Applications. - : Elsevier BV. - 0024-3795. ; 610, s. 673-697
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Tidskriftsartikel (refereegranskat)abstract
- As an indicator of the stability of spectral clustering of an undirected weighted graph into k clusters, the kth spectral gap of the graph Laplacian is often considered. The k-th spectral gap is characterized here as an unstructured distance to ambiguity, namely as the minimal distance of the Laplacian to arbitrary symmetric matrices with vanishing kth spectral gap. As a more appropriate measure of stability, the structured distance to ambiguity of the k-clustering is introduced as the minimal distance of the Laplacian to Laplacians of the same graph with weights that are perturbed such that the k-th spectral gap vanishes. To compute a solution to this matrix nearness problem, a two-level iterative algorithm is proposed that uses a constrained gradient system of matrix differential equations in the inner iteration and a one-dimensional optimization of the perturbation size in the outer iteration. The structured and unstructured distances to ambiguity are compared on some example graphs. The numerical experiments show, in particular, that selecting the number k of clusters according to the criterion of maximal stability can lead to different results for the structured and unstructured stability indicators.
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| 10. |
- Bazzani, Armando, et al.
(författare)
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NETWORK STRUCTURES DYNAMICS. An ecological application
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The network theory succeeded to apply the mathematical results of graph theory to describe the complex structures of big dataset provided by biological, economic and social systems. Recently the dynamical nature of the empirical observations has pointed out the necessity of introducing a dynamical structure on the considered interaction networks both to study the features of equilibrium solutions and to define new dynamical observables which allow to measure the resilience or frailty of the observed systems. We present a mathematical description of a network structure starting from the concept of landscape potential. Then we introduce a dynamics into this network structure by means of a Master Equation and we characterize some properties of the network using the eigenvalue spectral distribution of the associated stochastic matrix. In particular we are interested in the resilience of the stationary states and in the estimate relaxation time scales. Afterward we give some biological applications to understand the emergence of universal statistical laws as the relative species abundance distribution and the resilience of ecosystems.
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