Ashraf Ragab
University of Toulouse
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Publication
Featured researches published by Ashraf Ragab.
Journal of Biological Chemistry | 2003
Ashraf Ragab; Stéphane Bodin; Cécile Viala; Hugues Chap; Bernard Payrastre; Jeannie Ragab-Thomas
Human platelets express the receptor for immunoglobulin G, FcγRIIa, that triggers cell aggregation upon interaction with immune complexes. Here, we report that the rapid tyrosine phosphorylation of the Linker for Activation of T-cell (LAT) in human platelets stimulated by FcγRIIa cross-linking was followed by its complete dephosphorylation in an αIIb/β3 integrin-dependent manner. Concomitant to LAT dephosphorylation, the protein tyrosine phosphatase 1B (PTP1B) was activated through a mechanism involving its proteolysis by calpains downstream of integrins. Both PTP1B and LAT were associated with the actin cytoskeleton complex formed during platelet aggregation. Moreover, phospho-LAT appeared as a good substrate of activated PTP1B in vitro and these two proteins interacted upon platelet activation by FcγRIIa cross-linking. The permeant substrate-trapping PTP1B (TAT-PTP1B D181A) partly inhibited LAT dephosphorylation in human platelets, strongly suggesting that this tyrosine phosphatase was involved in this regulatory pathway. Using a pharmacological inhibitor, we provide evidence that PTP1B activation and LAT dephosphorylation processes were required for irreversible platelet aggregation. Altogether, our results demonstrate that PTP1B plays an important role in the integrin-mediated dephosphorylation of LAT in human platelets and is involved in the control of irreversible aggregation upon FcγRIIa stimulation.
Blood | 2010
Sylvie Giuriato; Marianne Foisseau; Emilie Dejean; Dean W. Felsher; Talal Al Saati; Cécile Demur; Ashraf Ragab; Anna Kruczynski; Claudine Schiff; Georges Delsol; Fabienne Meggetto
NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) and TPM3-ALK (nonmuscular tropomyosin 3-anaplastic lymphoma kinase) are oncogenic tyrosine kinases implicated in the pathogenesis of human ALK-positive lymphoma. We report here the development of novel conditional mouse models for ALK-induced lymphomagenesis, with the use of the tetracycline regulatory system under the control of the EmuSRalpha enhancer/promoter. The expression of either oncogene resulted in the arrest of the differentiation of early B cells and lymphomagenesis. We also observed the development of skin keratoacanthoma lesions, probably because of aberrant ALK expression in keratinocytes. The inactivation of the ALK oncogene on doxycycline treatment was sufficient to induce sustained regression of both hematopoietic tumors and skin disease. Importantly, treatment with the specific ALK inhibitor (PF-2341066) also reversed the pathologic states, showing the value of these mouse models for the validation of ALK tyrosine kinase inhibitors. Thus, our results show (1) that NPM-ALK and TPM3-ALK oncogenes are sufficient for lymphoma/leukemia development and required for tumor maintenance, hence validating ALK as potentially effective therapeutic target; and (2) for the first time, in vivo, the equal tumorigenic potential of the NPM-ALK and TPM3-ALK oncogenic tyrosine kinases. Our models offer a new tool to investigate in vivo the molecular mechanisms associated with ALK-induced lymphoproliferative disorders.
Journal of Biological Chemistry | 2001
Ama Gassama-Diagne; Françoise Hullin-Matsuda; Ruo Ya Li; Michel Nauze; Ashraf Ragab; Véronique Pons; Claire Delagebeaudeuf; Marie-Françoise Simon; Josette Fauvel; Hugues Chap
Enterocyte terminal differentiation occurs at the crypt-villus junction through the transcriptional activation of cell-specific genes, many of which code for proteins of the brush border membrane such as intestinal alkaline phosphatase, sucrase-isomaltase, or the microvillar structural protein villin. Several studies have shown that this sharp increase in specific mRNA levels is intimately associated with arrest of cell proliferation. We isolated several clones from a guinea pig intestine cDNA library. They encode new proteins characterized by an original structure associating a carboxyl-terminal B30.2/RFP-like domain and a long leucine zipper at the amino terminus. The first member of this novel gene family codes for a 65-kDa protein termed enterophilin-1, which is specifically expressed in enterocytes before their final differentiation. Enterophilin-1 is the most abundant in the small intestine but is still present in significant amounts in colonic enterocytes. In Caco-2 cells, a similar 65-kDa protein was recognized by a specific anti-enterophilin-1 antibody, and its expression was positively correlated with cell differentiation status. In addition, transfection of HT-29 cells with enterophilin-1 full-length cDNA slightly inhibited cell growth and promoted an increase in alkaline phosphatase activity. Taken together, these data identify enterophilins as a new family of proteins associated with enterocyte differentiation.
Blood | 2000
Marie-Pierre Gratacap; Jean-Pascal Herault; Cécile Viala; Ashraf Ragab; Pierre Savi; Jean-Marc Herbert; Hugues Chap; Monique Plantavid; Bernard Payrastre
Blood | 2007
Ashraf Ragab; Sonia Severin; Marie-Pierre Gratacap; Enrique Aguado; Marie Malissen; Martine Jandrot-Perrus; Bernard Malissen; Jeannie Ragab-Thomas; Bernard Payrastre
Blood | 2006
Jean-François Honorat; Ashraf Ragab; Laurence Lamant; Georges Delsol; Jeannie Ragab-Thomas
Thrombosis and Haemostasis | 2003
Stéphane Bodin; Cécile Viala; Ashraf Ragab; Bernard Payrastre
Journal of Biological Chemistry | 2001
Frédérique Paulhe; Ashraf Ragab; Corinne Albiges-Rizo; Hugues Chap; Niggi Iberg; Olivier Morand; Bertrand Perret
Journal of Biological Chemistry | 2001
Frédérique Paulhe; Claire Racaud-Sultan; Ashraf Ragab; Corinne Albiges-Rizo; Hugues Chap; Niggi Iberg; Olivier Morand; Bertrand Perret
Arteriosclerosis, Thrombosis, and Vascular Biology | 2018
Pierre-Alexandre Laurent; Béatrice Hechler; Romain Solinhac; Ashraf Ragab; Cendrine Cabou; Typhaine Anquetil; Sonia Severin; Cécile V. Denis; Pierre H. Mangin; Bart Vanhaesebroeck; Bernard Payrastre; Marie-Pierre Gratacap