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Article Dans Une Revue Médecine/Sciences Année : 2007

Gas-6 and protein S: vitamin K-dependent factors and ligands for the TAM tyrosine kinase receptors family

Fonctions nouvelles de Gas-6 et de la protéine S

Résumé

The gamma-carboxyglutamate-containing proteins are a family of secreted vitamin K-dependent proteins in which some glutamyl residues are post-translationally modified to gamma-carboxyglutamic acid residues. A vitamin K-dependent gamma-glutamyl carboxylase enzyme catalyses this post-translational modification. The gamma-carboxylase reaction requires vitamin K in its reduced form, vitamin K hydroquinone, and generates gamma-carboxyglutamate and vitamin K 2,3,-epoxide which is then recycled back to the hydroquinone form by a vitamin K reductase system. Warfarin blocks the vitamin K cycle and hence inhibits the gamma-carboxylase reaction, and this property of Warfarin has led to its wide use in anticoagulant therapy. Until recently, interest in vitamin K-dependent proteins was mostly restricted to the field of hematology. However, the discovery that the anti-coagulant factor protein S and its structural homologue Gas6 (growth arrest-specific gene 6), two vitamin K-dependent proteins, are ligands for the Tyro3/Axl/Mer family of related tyrosine kinase receptors has opened up a new area of research. Moreover, the phenotypes associated with the invalidation of genes encoding vitamin K-dependent proteins or their receptors revealed their implication in regulating phagocytosis during many cell differentiation phenomena such as retinogenesis, neurogenesis, osteogenesis, and spermatogenesis. Additionally, protein S was identified as the major factor responsible for serum-stimulated phagocytosis of apoptotic cells. Therefore, the elucidation of the molecular mechanisms underlying the role of vitamin K-dependent proteins in regulating apoptotic cell phagocytosis may lead to a better understanding of the physiopathology of cell differentiation and could form the framework of new therapeutic strategies aiming at a selective targeting of cell phagocytosis associated pathologies.

Dates et versions

hal-00413569 , version 1 (04-09-2009)

Identifiants

Citer

Omar Benzakour, Aurore Gely, Romain Lara, Valérie Coronas. Fonctions nouvelles de Gas-6 et de la protéine S : Facteurs vitamine K-dépendants et ligands des récepteurs tyrosine kinase de la famille TAM. Médecine/Sciences, 2007, 23 (10), pp.826-833. ⟨10.1051/medsci/20072310826⟩. ⟨hal-00413569⟩
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