Institution
University of Dundee
Education•Dundee, United Kingdom•
About: University of Dundee is a education organization based out in Dundee, United Kingdom. It is known for research contribution in the topics: Population & Protein kinase A. The organization has 19258 authors who have published 39640 publications receiving 1919433 citations. The organization is also known as: Universitas Dundensis & Dundee University.
Papers published on a yearly basis
Papers
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TL;DR: The structure of the core heterotrimeric L KB1-STRADα-MO25α complex is described, revealing an unusual allosteric mechanism of LKB1 activation and how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB 1 function.
Abstract: The LKB1 tumor suppressor is a protein kinase that controls the activity of adenosine monophosphate–activated protein kinase (AMPK). LKB1 activity is regulated by the pseudokinase STRADα and the scaffolding protein MO25α through an unknown, phosphorylation-independent, mechanism. We describe the structure of the core heterotrimeric LKB1-STRADα-MO25α complex, revealing an unusual allosteric mechanism of LKB1 activation. STRADα adopts a closed conformation typical of active protein kinases and binds LKB1 as a pseudosubstrate. STRADα and MO25α promote the active conformation of LKB1, which is stabilized by MO25α interacting with the LKB1 activation loop. This previously undescribed mechanism of kinase activation may be relevant to understanding the evolution of other pseudokinases. The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function.
323 citations
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TL;DR: The FFIT programme can help a large proportion of men to lose a clinically important amount of weight; it offers one effective strategy to challenge male obesity.
323 citations
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TL;DR: Although the understanding of the insulin signal transduction pathway is far from being complete, current knowledge of this pathway provides a framework for the development of novel drugs to treat diabetes and it is possible that drugs that mimic the effect that insulin has on its signalling pathway are orally effective.
322 citations
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TL;DR: The recently discovered non-mevalonate biosynthetic route to isoprenoid precursors is an essential metabolic pathway in plants, apicomplexan parasites, and many species of bacteria.
322 citations
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TL;DR: Genetic evidence is provided that PDK1 is essential for mouse embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin's ability to activate PKB, S6K and RSK.
Abstract: PDK1 functions as a master kinase, phosphorylating and activating PKB/Akt, S6K and RSK. To learn more about the roles of PDK1, we generated mice that either lack PDK1 or possess PDK1 hypomorphic alleles, expressing only approximately 10% of the normal level of PDK1. PDK1(-/-) embryos die at embryonic day 9.5, displaying multiple abnormalities including lack of somites, forebrain and neural crest derived tissues; however, development of hind- and midbrain proceed relatively normally. In contrast, hypomorphic PDK1 mice are viable and fertile, and insulin injection induces the normal activation of PKB, S6K and RSK. Nevertheless, these mice are 40-50% smaller than control animals. The organ volumes from the PDK1 hypomorphic mice are reduced proportionately. We also establish that the volume of a number of PDK1-deficient cells is reduced by 35-60%, and show that PDK1 deficiency does not affect cell number, nuclear size or proliferation. We provide genetic evidence that PDK1 is essential for mouse embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin's ability to activate PKB, S6K and RSK.
321 citations
Authors
Showing all 19404 results
Name | H-index | Papers | Citations |
---|---|---|---|
Matthias Mann | 221 | 887 | 230213 |
Mark I. McCarthy | 200 | 1028 | 187898 |
Stefan Schreiber | 178 | 1233 | 138528 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Salvador Moncada | 164 | 495 | 138030 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Andrew P. McMahon | 162 | 415 | 90650 |
Philip Cohen | 154 | 555 | 110856 |
Dirk Inzé | 149 | 647 | 74468 |
Andrew T. Hattersley | 146 | 768 | 106949 |
Antonio Lanzavecchia | 145 | 408 | 100065 |
Kim Nasmyth | 142 | 294 | 59231 |
David Price | 138 | 1687 | 93535 |
Dario R. Alessi | 136 | 354 | 74753 |