Integrin cytoplasmic tyrosine motif is required for outside-in alphaIIbbeta3 signalling and platelet function.

来自 EBSCO

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作者：

D.A. Law，F.R. DeGuzman，P Heiser，K Ministri-Madrid，D.R. Phillips

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摘要：

Integrins not only bind adhesive ligands, they also act as signalling receptors. Both functions allow the integrin alphaIIbbeta3 to mediate platelet aggregation. Platelet activate alphaIIbbeta3 (inside-out signalling) to allow the of soluble . Subsequent platelet aggregation leads to outside-in alphaIIbbeta3 signalling, which results in , tyrosine of numerous proteins including beta3 itself, increased cytoskeletal reorganisation and further activation of alphaIIbbeta3. Thus, outside-in signals enhance aggregation, although the mechanisms and functional consequences of specific signalling events remain unclear. Here we describe a that expresses an alphaIIbbeta3 in which the tyrosines in the integrin cytoplasmic tyrosine motif have been mutated to phenylalanines. These are selectively impaired in outside-in alphaIIbbeta3 signalling, with defective aggregation and clot-retraction responses in vitro, and an in vivo bleeding defect which is characterized by a pronounced tendency to rebleed. These data provide evidence for an important role of outside-in signalling in platelet physiology. Furthermore, they identify the integrin cytoplasmic tyrosine motif as a key mediator of beta-integrin signals and a potential target for new therapeutic agents.

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关键词：

Animals Mice Blood Platelets Cytoplasm Tyrosine Fibrinogen Platelet Glycoprotein GPIIb-IIIa Complex Cloning, Molecular Bleeding Time Blood Coagulation