JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera through an EpoR-independent Rap1/Akt pathway.: JAK2V617F activates Lu/BCAM through Rap1/Akt

Maria De Grandis 1, 2 Marie Cambot 3 Marie-Paule Wautier 2, 1 Bruno Cassinat 4 Christine Chomienne 4, 5 Yves Colin 1, 2 Jean-Luc Wautier 1, 2 Caroline Le van Kim 1, 2 Wassim El Nemer 1, 2, *
* Auteur correspondant
1 Protéines de la membrane érythrocytaire et homologues non-érythroides
2 GR-Ex
3 INTS - Institut National de la Transfusion Sanguine [Paris]
4 Unite de Biologie Cellulaire
5 Hématologie -Immunologie -Cibles thérapeutiques
Abstract : Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
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Article dans une revue
Blood, American Society of Hematology, 2013, 121 (4), pp.658-65. 〈10.1182/blood-2012-07-440487〉
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http://www.hal.inserm.fr/inserm-00821109
Contributeur : Wassim El Nemer <>
Soumis le : mardi 7 mai 2013 - 15:02:29
Dernière modification le : jeudi 15 novembre 2018 - 20:27:27

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Maria De Grandis, Marie Cambot, Marie-Paule Wautier, Bruno Cassinat, Christine Chomienne, et al.. JAK2V617F activates Lu/BCAM-mediated red cell adhesion in polycythemia vera through an EpoR-independent Rap1/Akt pathway.: JAK2V617F activates Lu/BCAM through Rap1/Akt. Blood, American Society of Hematology, 2013, 121 (4), pp.658-65. 〈10.1182/blood-2012-07-440487〉. 〈inserm-00821109〉

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