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Migration of megakaryocytes (MKs) from the proliferative osteoblastic niche to the capillary-rich vascular niche is essential for proplatelet formation and platelet release. In this study, we explore the role of surface glycoprotein receptors and signaling proteins in regulating MK migration and platelet recovery after immune-induced thrombocytopenia. We show that spreading and migration of mouse primary bone marrow-derived MKs on a fibronectin matrix are abolished by the Src family kinases inhibitor PP1, the Syk kinase inhibitor R406 and the integrin alphaIIbbeta3 antagonist lotrafiban. We also demonstrate that these responses are inhibited in primary phospholipase C gamma2 (PLCgamma2)-deficient MKs. Conversely, MK spreading and migration were unaltered in the absence of the collagen receptor, the glycoprotein VI-FcRgamma-chain complex. We previously reported a correlation between a defect in MK migration and platelet recovery in the absence of platelet endothelial cell adhesion molecule-1 and the tyrosine phosphatase CD148. This correlation also holds for mice deficient in PLCgamma2. This study identifies a model in which integrin signaling via Src family kinases and Syk kinase to PLCgamma2 is required for MK spreading, migration, and platelet formation.

Original publication

DOI

10.1182/blood-2010-03-275990

Type

Journal article

Journal

Blood

Publication Date

05/08/2010

Volume

116

Pages

793 - 800

Keywords

Animals, Benzodiazepines, Blood Platelets, Cell Movement, Cell Shape, Cells, Cultured, Intracellular Signaling Peptides and Proteins, Megakaryocytes, Mice, Mice, Inbred C57BL, Mice, Knockout, Oxazines, Phospholipase C gamma, Phosphorylation, Piperidines, Platelet Glycoprotein GPIIb-IIIa Complex, Protein Kinase Inhibitors, Protein Processing, Post-Translational, Protein-Tyrosine Kinases, Proto-Oncogene Proteins pp60(c-src), Purpura, Thrombocytopenic, Idiopathic, Pyrazoles, Pyridines, Pyrimidines, Signal Transduction, Syk Kinase, Thrombopoiesis