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

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  • معلومة اضافية
    • Contributors:
      Protéines de la membrane érythrocytaire et homologues non-érythroides (U665); Université des Antilles et de la Guyane (UAG)-Institut National de la Transfusion Sanguine Paris (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM); GR-Ex; Laboratoire d'Excellence; Institut National de la Transfusion Sanguine Paris (INTS); Unite de Biologie Cellulaire; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Hématologie -Immunologie -Cibles thérapeutiques; Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM); The work was funded by the Institut National de la Santé et de la Recherche Médicale (Inserm), the Institut National de la Transfusion Sanguine (INTS), and a grant from Région Île-de-France (SESAME 2007 no. F-08-1104/R). The PhD student, Maria De Grandis, was funded by the Ministère de l'Enseignement Supérieur et de la Recherche at the Ecole Doctorale B3MI.
    • بيانات النشر:
      HAL CCSD
      American Society of Hematology
    • الموضوع:
      2013
    • نبذة مختصرة :
      International audience ; 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.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/23160466; inserm-00821109; https://inserm.hal.science/inserm-00821109; https://inserm.hal.science/inserm-00821109/document; https://inserm.hal.science/inserm-00821109/file/De_Grandis_Blood_2013.pdf; PUBMED: 23160466
    • الرقم المعرف:
      10.1182/blood-2012-07-440487
    • Rights:
      info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.E9C50FAB