scholarly journals Modular evolution of phosphorylation-based signalling systems

2012 ◽  
Vol 367 (1602) ◽  
pp. 2540-2555 ◽  
Author(s):  
Jing Jin ◽  
Tony Pawson

Phosphorylation sites are formed by protein kinases (‘writers’), frequently exert their effects following recognition by phospho-binding proteins (‘readers’) and are removed by protein phosphatases (‘erasers’). This writer–reader–eraser toolkit allows phosphorylation events to control a broad range of regulatory processes, and has been pivotal in the evolution of new functions required for the development of multi-cellular animals. The proteins that comprise this system of protein kinases, phospho-binding targets and phosphatases are typically modular in organization, in the sense that they are composed of multiple globular domains and smaller peptide motifs with binding or catalytic properties. The linkage of these binding and catalytic modules in new ways through genetic recombination, and the selection of particular domain combinations, has promoted the evolution of novel, biologically useful processes. Conversely, the joining of domains in aberrant combinations can subvert cell signalling and be causative in diseases such as cancer. Major inventions such as phosphotyrosine (pTyr)-mediated signalling that flourished in the first multi-cellular animals and their immediate predecessors resulted from stepwise evolutionary progression. This involved changes in the binding properties of interaction domains such as SH2 and their linkage to new domain types, and alterations in the catalytic specificities of kinases and phosphatases. This review will focus on the modular aspects of signalling networks and the mechanism by which they may have evolved.

Author(s):  
Li Wu ◽  
Yilin Lyu ◽  
Pingping Wu ◽  
Tongyu Luo ◽  
Junyuan Zeng ◽  
...  

Kluyveromyces marxianus is the fastest-growing eukaryote and a promising host for producing bioethanol and heterologous proteins. To perform a laboratory evolution of thermal tolerance in K. marxianus, diploid, triploid and tetraploid strains were constructed, respectively. Considering the genetic diversity caused by genetic recombination in meiosis, we established an iterative cycle of “diploid/polyploid - meiosis - selection of spores at high temperature” to screen thermotolerant strains. Results showed that the evolution of thermal tolerance in diploid strain was more efficient than that in triploid and tetraploid strains. The thermal tolerance of the progenies of diploid and triploid strains after a two-round screen was significantly improved than that after a one-round screen, while the thermal tolerance of the progenies after the one-round screen was better than that of the initial strain. After a two-round screen, the maximum tolerable temperature of Dip2-8, a progeny of diploid strain, was 3°C higher than that of the original strain. Whole-genome sequencing revealed nonsense mutations of PSR1 and PDE2 in the thermotolerant progenies. Deletion of either PSR1 or PDE2 in the original strain improved thermotolerance and two deletions displayed additive effects, suggesting PSR1 and PDE2 negatively regulated the thermotolerance of K. marxianus in parallel pathways. Therefore, the iterative cycle of “meiosis - spore screening” developed in this study provides an efficient way to perform the laboratory evolution of heat resistance in yeast.


2010 ◽  
Vol 433 (2) ◽  
pp. e1-e2 ◽  
Author(s):  
Zachary A. Knight

More than 20 protein kinases are directly activated by 3-phosphoinositide-dependent kinase 1 (PDK1), which is a central component of the pathways that regulate cell growth, proliferation and survival. Despite the importance of PDK1 in cell signalling, highly selective PDK1 inhibitors have not been described. In this issue of the Biochemical Journal, Dario Alessi's group and their collaborators at GlaxoSmithKline report GSK2334470, a potent and selective PDK1 inhibitor. They show that this compound blocks the phosphorylation of known PDK1 substrates, but surprisingly find that the potency and kinetics of inhibition vary for different PDK1 targets. This substrate-specific inhibition has implications for the development of PDK1 inhibitors as drugs.


Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 229 ◽  
Author(s):  
Andrea Arrones ◽  
Santiago Vilanova ◽  
Mariola Plazas ◽  
Giulio Mangino ◽  
Laura Pascual ◽  
...  

The compelling need to increase global agricultural production requires new breeding approaches that facilitate exploiting the diversity available in the plant genetic resources. Multi-parent advanced generation inter-cross (MAGIC) populations are large sets of recombinant inbred lines (RILs) that are a genetic mosaic of multiple founder parents. MAGIC populations display emerging features over experimental bi-parental and germplasm populations in combining significant levels of genetic recombination, a lack of genetic structure, and high genetic and phenotypic diversity. The development of MAGIC populations can be performed using “funnel” or “diallel” cross-designs, which are of great relevance choosing appropriate parents and defining optimal population sizes. Significant advances in specific software development are facilitating the genetic analysis of the complex genetic constitutions of MAGIC populations. Despite the complexity and the resources required in their development, due to their potential and interest for breeding, the number of MAGIC populations available and under development is continuously growing, with 45 MAGIC populations in different crops being reported here. Though cereals are by far the crop group where more MAGIC populations have been developed, MAGIC populations have also started to become available in other crop groups. The results obtained so far demonstrate that MAGIC populations are a very powerful tool for the dissection of complex traits, as well as a resource for the selection of recombinant elite breeding material and cultivars. In addition, some new MAGIC approaches that can make significant contributions to breeding, such as the development of inter-specific MAGIC populations, the development of MAGIC-like populations in crops where pure lines are not available, and the establishment of strategies for the straightforward incorporation of MAGIC materials in breeding pipelines, have barely been explored. The evidence that is already available indicates that MAGIC populations will play a major role in the coming years in allowing for impressive gains in plant breeding for developing new generations of dramatically improved cultivars.


2010 ◽  
Vol 430 (3) ◽  
pp. e5-e6 ◽  
Author(s):  
Iakov N. Rudenko ◽  
Mark R. Cookson

Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of familial PD (Parkinson’s disease). Mutations that cause PD are found in either the GTPase or kinase domains of LRRK2 or an intervening sequence called the COR [C-terminus of ROC (Ras of complex proteins)] domain. As well as the two catalytic domains, LRRK2 possesses several protein–protein interaction domains, but their function and the proteins with which they interact are poorly understood. In this issue of the Biochemical Journal, Nichols et al. study the interaction of the N-terminal region of LRRK2 with 14-3-3 proteins, regulatory proteins that often bind to phosphorylated regions of components of cell signalling pathways. Using a combination of techniques, Nichols et al. have identified two residues (Ser910 and Ser935) that are critically responsible for 14-3-3 binding. The interaction of LRRK2 with 14-3-3 proteins can prevent dephosphorylation of Ser910/Ser935 and stabilize LRRK2 structure, perhaps by influencing the dimerization of LRRK2. The ability to interact with 14-3-3 correlates with the pattern of intracellular LRRK2 distribution. Collectively, these new results identify a potentially important regulatory mechanism of this complex protein and might provide ways to think about therapeutic opportunities for PD.


2017 ◽  
Vol 372 (1713) ◽  
pp. 20150477 ◽  
Author(s):  
Leslie S. Babonis ◽  
Mark Q. Martindale

Communication among cells was paramount to the evolutionary increase in cell type diversity and, ultimately, the origin of large body size. Across the diversity of Metazoa, there are only few conserved cell signalling pathways known to orchestrate the complex cell and tissue interactions regulating development; thus, modification to these few pathways has been responsible for generating diversity during the evolution of animals. Here, we summarize evidence for the origin and putative function of the intracellular, membrane-bound and secreted components of seven metazoan cell signalling pathways with a special focus on early branching metazoans (ctenophores, poriferans, placozoans and cnidarians) and basal unikonts (amoebozoans, fungi, filastereans and choanoflagellates). We highlight the modular incorporation of intra- and extracellular components in each signalling pathway and suggest that increases in the complexity of the extracellular matrix may have further promoted the modulation of cell signalling during metazoan evolution. Most importantly, this updated view of metazoan signalling pathways highlights the need for explicit study of canonical signalling pathway components in taxa that do not operate a complete signalling pathway. Studies like these are critical for developing a deeper understanding of the evolution of cell signalling. This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’.


Comunicar ◽  
2005 ◽  
Vol 13 (25) ◽  
Author(s):  
Glaucia Guimarães ◽  
Nilda Alves ◽  
Raquel Goulart-Barreto

Based on hints gathered in documents and observations, the aim of this work is to reveal emancipatory meanings present, though invisible or not fully realized in regulatory processes, as well as to understand knowledge and ideas impregnated in the daily practices of social agents. In order to valorize edge knowledge and social practices, this work is grounded on Boaventura de Sousa Santos, especially on his formulation of a two-fold Sociology: one related to the social experiences that have not been recognized yet as valuable and the second related to the expansion of possible social experiences. The movement corresponds to the construction of an archeology of already developed social experiences, though not visible or recognized by the existing theoretical frameworks, so as to reveal both kinds of experiences: the recognized ones and the possible ones. By means of experiences developed by ordinary people, the aim is to get to know and socialize experiences conducted in boundary scientific works in several social areas to make it possible to gather hints to the production of alternatives to hegemonic ideas and to the maintenance of traditions abandoned by modern sciences. Based on what can be called «Sociology of absences», experiences can be valued, publicized and used to convey hidden meanings, to exploit possible ways to deal with posed questions and to legitimate new forms of thinking. Based on these assumptions, we present a reflection on an experience in the social field, regarding possible conflicts and dialogues between forms of knowledge. In this case, we treat the pedagogical experience with video and TV programs, developed by teachers and experts on education and communication in the official schools of Rio de JaneiroCity, being the latter put in charge of helping the former in their pedagogical practices. By means of the hints gathered, sometimes taken as unimportant, it was possible to identify in the teachers´ speeches and actions, particular ways to work works with video and TV programs that, far from being characterized by lack of knowledge, were plenty of alternative logical thinking and could lead to the production of creative and emancipatory practices. In short, what could be seen as meaningless could also be regarded as emerging knowledge. Com base em indícios resgatados em documentos e observações, o objetivo deste trabalho é revelar sentidos emancipatórios existentes, mas invisíveis ou ignorados, em meio aos processos regulatórios, bem como compreender os saberes, as idéias que impregnam as práticas cotidianas desenvolvidas pelos sujeitos sociais. No sentido de valorizar os conhecimentos e as práticas sociais marginais, fundamentamo-nos em Boaventura de Sousa Santos, que propõe a sociologia das ausências e a sociologia das emergências. Na primeira, o movimento é o de expandir o domínio das experiências sociais já disponíveis, contudo negligenciadas, enquanto na segunda é o de expandir o domínio das experiências sociais possíveis. Propõe uma arqueologia das experiências já existentes, mas invisíveis, no intuito de revelar as experiências do mundo, tanto as disponíveis como as possíveis. Trata-se de revelar e difundir experiências vividas por pessoas comuns, de conhecer e propalar experiências construídas em trabalhos científicos marginalizados e de encontrar e anunciar conhecimentos/experiências nos mais diversos campos sociais, no movimento de constituição de alternativas à lógica hegemônica e, ao mesmo tempo, de manutenção de tradições marginalizadas e desperdiçadas pela ciência moderna. Por meio da sociologia das ausências, estas experiências são resgatadas e divulgadas para se tornarem possíveis encaminhamentos das questões enfrentadas, para se constituírem em outros sentidos para a transformação social ou, ainda, para propor novas formas de pensar. Apresentamos uma reflexão sobre experiência no campo social de conhecimentos que, segundo Santos, trata de conflitos e diálogos possíveis entre diferentes formas de conhecimento. No caso deste trabalho, a tentativa é a de resgatar a experiência pedagógica no uso de vídeos de alguns dos professores da Rede Municipal de Educação do Rio de Janeiro, ignorada pelos próprios professores e por especialistas nas áreas de educação e comunicação, sendo os últimos produtores de vídeos educativos para auxiliar a prática pedagógica dos primeiros. O exercício de ler indícios e pistas, muitas vezes insignificantes, mas reveladores, presentes nas falas e ações dos professores, indicou que, longe de ausência de saber, os modos peculiares de utilização de TV e vídeo revelam outros saberes e outra(s) lógica(s). O que pode sugerir ação isolada e desprovida de conhecimento, também pode ser compreendido como pista para uma prática e um saber criativo e emancipatório.


Sign in / Sign up

Export Citation Format

Share Document