Manioc : Portail | resultats 141 - 160 pour la recherche: Philips, Richard

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The Ras/Raf/MEK/ERK signaling pathway is involved in essential cell processes and it is abnormally activated in similar to 30 % of cancers and cognitive disorders. Two ERK isoforms have been described, ERK1 and ERK2; ERK2 being regarded by many as essential due to the embryonic lethality of ERK2 knock-out mice, whereas mice lacking ERK1 are viable and fertile. The controversial question of why we have two ERKs and whether they have differential functions or display functional redundancy has not yet been resolved. Results: To investigate this question we used a novel approach based on comparing the evolution of ERK isoforms' sequences and protein expression across vertebrates. We gathered and cloned erk1 and erk2 coding sequences and we examined protein expression of isoforms in brain extracts in all major clades of vertebrate evolution. For the first time, we measured each isoforms' relative protein level in phylogenetically distant animals using anti-phospho antibodies targeting active ERKs. We demonstrate that squamates (lizards, snakes and geckos), despite having both genes, do not express ERK2 protein whereas other tetrapods either do not express ERK1 protein or have lost the erk1 gene. To demonstrate the unexpected squamates' lack of ERK2 expression, we targeted each ERK isoform in lizard primary fibroblasts by specific siRNA-mediated knockdown. We also found that undetectable expression of ERK2 in lizard is compensated by a greater strength of lizard's erk1 promoter. Finally, phylogenetic analysis revealed that ERK1 amino acids sequences evolve faster than ERK2' s likely due to genomic factors, including a large difference in gene size, rather than from functional differences since amino acids essential for function are kept invariant. Conclusions: ERK isoforms appeared by a single gene duplication at the onset of vertebrate evolution at least 400 Mya. Our results demonstrate that tetrapods can live by expressing either one or both ERK isoforms, supporting the notion that ERK1/2 act interchangeably. Substrate recognition sites and catalytic cleft are nearly invariant in all vertebrate ERKs further suggesting functional redundancy. We suggest that future ERK research should shift towards understanding the role and regulation of total ERK quantity, especially in light of newly described erk2 gene amplification identified in tumors.
ISSN: 1471-2148

hal-01546165
https://hal.archives-ouvertes.fr/hal-01546165
DOI : 10.1186/s12862-015-0450-x

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Les colonies françaises
Auteur(s) : Gaffarel, Paul (1843-1920)
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Flora brasiliensis : enumeratio plantarum in Brasilia hactenus detectarum quas suis aliorumque botanicorum studiis descriptas et methodo naturali digestas partim icone illustratas. Volumen XIII, Pars II
Auteur(s) : Hegelmaier, Christoph Friedrich (1833-1906) Warming, Eugenius (1841-1924) Micheli, Marc (1844-1902) Koehne, Emil (1848-1918) Kanitz, Agoston (1843-1896)
Auteurs secondaires : Martius, Karl Friedrich Philipp von (1794-1868) Eichler, August Wilhelm (1837-1887)
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Almanach américain, ou Etat physique, politique, ecclésiastique et militaire de l'Amérique : ouvrage qui comprend les forces, la population, les loix, le commerce et l'administration de chaque province de cette partie du monde ; le tableau de ceux qui y figurent par leurs charges et par leurs dignités ; celui de la marine des peuples européens qui y ont possessions, et le nom des officiers qui sont employés dans cette partie de l'administration publique
Auteur(s) : Poncelin de la Roche-Tilhac, Jean-Charles (1746-1828)
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Flora brasiliensis : enumeratio plantarum in Brasilia hactenus detectarum quas suis aliorumque botanicorum studiis descriptas et methodo naturali digestas partim icone illustratas. Volumen XIII, Pars I
Auteur(s) : Martius, Carl Friedrich Philipp von (1794-1868) Eichler, August Wilhelm (1837-1887) Masters, Maxwell Tylden (1833-1907)
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Histoire générale des Antilles. Tome quatrième et premier de la deuxieme série
Auteur(s) : Dessalles, Adrien (1809-1870)
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Mélanges de littérature. [Volume 4]; Tome premier
Auteur(s) : Suard, Jean-Baptiste-Antoine (1732-1817)
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Flora brasiliensis : enumeratio plantarum in Brasilia hactenus detectarum quas suis aliorumque botanicorum studiis descriptas et methodo naturali digestas partim icone illustratas. Volumen XIV, Pars III, Melastomaceae : Tribus I, Microlicieae, Tribus II, Tibouchineae
Auteur(s) : Cogniaux, Alfred (1841-1916)
Auteurs secondaires : Martius, Karl Friedrich Philipp von (1794-1868) Eichler, August Wilhelm (1837-1887)
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Collection des constitutions, chartes et lois fondamentales des peuples de l'Europe et des deux Amériques. Tome V, [Espagne, Portugal, Haïti, États-Unis]
Auteur(s) : Dufaud, Pierre-Armand (1795-1877) Duvergier, Jean-Baptiste (1792-1877) Guadet, Joseph (1795-1887)
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