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All in the Family: Primary Megakaryocytes for Studies of Platelet aIIbb3 Signaling

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2001: 86/1 (July, State of the Art) pp.1-508
Pages: 259-65

All in the Family: Primary Megakaryocytes for Studies of Platelet aIIbb3 Signaling

Sanford J. Shattil (1), (2) , Andrew D. Leavitt (3)
Departments of (1) Vascular Biology and (2) Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, (3) Departments of Laboratory Medicine and Internal Medicine, The University of California at San Francisco, San Francisco, C


Integrin aIIbb3 mediates key platelet adhesive responses during hemostasis and thrombosis. Adhesive ligand binding to aIIbb3 is regulated by "inside-out" signals, while adhesion-dependent cytoskeletal events are regulated by "outside-in" signals from aIIbb3. Currently, the molecular basis of bidirectional aIIbb3 signaling is incompletely understood. The functional assessment of integrin signaling pathways in nucleated cells has been facilitated by techniques such as viral transduction which enable expression of dominant-active and dominantinhibitory gene products. This approach cannot be used with anucleate platelets. However, recent advances in the ability to expand human and murine megakaryocytes from hematopoietic stem cells provide a tractable and genetically manipulatable system for studies of aIIbb3 signaling. This overview will discuss some of the advantages and limitations of this approach and provide examples of its utility. Thus, in addition to their intrinsic value for understanding hematopoiesis and platelet formation, primary megakaryocytes represent a model system complementary to platelets for unraveling the remaining mysteries of aIIbb3 signaling.