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SHP2 : une cible potentielle d’intérêt dans l’obésité et ses complications métaboliques ?

SHP2: a possible target of interest in obesity and its metabolic complications?

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Obésité

Résumé

SHP2 est une protéine ubiquitaire qui appartient à la famille très conservée au cours de l’évolution des protéines tyrosine phosphatases (PTP). Les données accumulées depuis sa découverte lui confèrent des rôles majeurs dans la régulation de multiples voies de signalisation dépendantes des tyrosine-kinases qui lui permettent de contrôler des processus cellulaires clés tels que la prolifération, la différenciation, la survie ou le métabolisme énergétique. L’importance de SHP2 dans la physiologie cellulaire s’illustre notamment par les conséquences létales de son inactivation dans divers organismes et l’impact de sa délétion ciblée sur le développement et la fonction de nombreux organes. En particulier, SHP2 apparaît comme un régulateur majeur de différents aspects du métabolisme énergétique en contrôlant à la fois le développement du tissu adipeux, la balance énergétique ou l’homéostasie glucidique. Ces vingt dernières années, l’étude de SHP2 a suscité un intérêt grandissant avec la découverte de maladies génétiques causées par des mutations « gain de fonction » ou « perte de fonction » de cette phosphatase, qui conduisent, chez l’Homme, à des défauts de développement, à certains cancers, et qui pourraient aussi impacter le métabolisme énergétique.

Dans cette revue, nous présenterons les principaux rôles physiologiques de SHP2, en nous focalisant plus particulièrement sur la place qu’elle tient dans la régulation du métabolisme énergétique, puis nous aborderons les conséquences physiopathologiques de sa dérégulation chez l’Homme, en particulier en termes de perturbations métaboliques.

Abstract

SHP2 is a ubiquitous protein belonging to the evolutionary-conserved protein tyrosine phosphatases (PTP) family. Data accumulated since its discovery confer on SHP2 major roles in regulating multiple tyrosine kinase-dependent signaling pathways, which control key cellular processes, notably proliferation, differentiation, survival or energy metabolism. Thus, the lethal outcomes of SHP2 inactivation in various organisms, as well as the impacts of its targeted deletion on the development and/or function of numerous organs and tissues, highlight SHP2’s significance in cell physiology. In particular, SHP2 has been proved to be a major regulator of different aspects of energy metabolism, as it concurrently controls adipose tissue development, energy balance and carbohydrate/lipid homeostasis. Over the past two decades, SHP2 study has aroused a growing interest, with the discovery of genetic diseases caused by « gain-of-function » or « loss-of-function » mutations of this phosphatase, that result in Human in developmental defects, certain cancers, and could also affect energy metabolism.

In this review, we summarize the main physiological roles of SHP2, with a particular focus on its function in energy metabolism regulation, and then describe the pathophysiological consequences of its deregulation in human diseases, notably in term of metabolism imbalance.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Toulouse, France

    M. Tajan, P. Valet & A. Yart

  2. Université de Toulouse, Université Paul Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France

    M. Tajan, P. Valet & A. Yart

  3. Unité de Génétique, Endocrinologie et Maladies Osseuses, Hôpital des Enfants, CHU Purpan, Toulouse, France

    T. Edouard

  4. Institut National de la Santé et de la Recherche Médicale (INSERM), U1043, Toulouse, France

    T. Edouard

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Tajan, M., Edouard, T., Valet, P. et al. SHP2 : une cible potentielle d’intérêt dans l’obésité et ses complications métaboliques ?. Obes 11, 23–33 (2016). https://doi.org/10.1007/s11690-015-0511-8

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