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Dive into the research topics where Ashraf Ragab is active.

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Featured researches published by Ashraf Ragab.


Journal of Biological Chemistry | 2003

The Tyrosine Phosphatase 1B Regulates Linker for Activation of T-cell Phosphorylation and Platelet Aggregation upon FcγRIIa Cross-linking

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

Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B-cell lymphoma/leukemia

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

Enterophilins, a New Family of Leucine Zipper Proteins Bearing a B30.2 Domain and Associated with Enterocyte Differentiation

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

FcγRIIA requires a Gi-dependent pathway for an efficient stimulation of phosphoinositide 3-kinase, calcium mobilization, and platelet aggregation

Marie-Pierre Gratacap; Jean-Pascal Herault; Cécile Viala; Ashraf Ragab; Pierre Savi; Jean-Marc Herbert; Hugues Chap; Monique Plantavid; Bernard Payrastre


Blood | 2007

Roles of the C-terminal tyrosine residues of LAT in GPVI-induced platelet activation: insights into the mechanism of PLCγ2 activation

Ashraf Ragab; Sonia Severin; Marie-Pierre Gratacap; Enrique Aguado; Marie Malissen; Martine Jandrot-Perrus; Bernard Malissen; Jeannie Ragab-Thomas; Bernard Payrastre


Blood | 2006

SHP1 tyrosine phosphatase negatively regulates NPM-ALK tyrosine kinase signaling

Jean-François Honorat; Ashraf Ragab; Laurence Lamant; Georges Delsol; Jeannie Ragab-Thomas


Thrombosis and Haemostasis | 2003

A critical role of lipid rafts in the organization of a key FcγRIIa-mediated signaling pathway in human platelets

Stéphane Bodin; Cécile Viala; Ashraf Ragab; Bernard Payrastre


Journal of Biological Chemistry | 2001

Differential regulation of phosphoinositide metabolism by alphaVbeta3 and alphaVbeta5 integrins upon smooth muscle cell migration.

Frédérique Paulhe; Ashraf Ragab; Corinne Albiges-Rizo; Hugues Chap; Niggi Iberg; Olivier Morand; Bertrand Perret


Journal of Biological Chemistry | 2001

Differential regulation of phosphoinositides metabolism by alphaVbeta3 and alphaVbeta5 integrins upon smooth muscle cell migration

Frédérique Paulhe; Claire Racaud-Sultan; Ashraf Ragab; Corinne Albiges-Rizo; Hugues Chap; Niggi Iberg; Olivier Morand; Bertrand Perret


Arteriosclerosis, Thrombosis, and Vascular Biology | 2018

Impact of PI3Kα (Phosphoinositide 3-Kinase Alpha) Inhibition on Hemostasis and Thrombosis

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

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Bernard Payrastre

Witten/Herdecke University

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Marie-Pierre Gratacap

French Institute of Health and Medical Research

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