NDLI: activation and stable fibrinogen binding 3 β IIb α ADAP interactions with talin and kindlin promote platelet integrin

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activation and stable fibrinogen binding 3 β IIb α ADAP interactions with talin and kindlin promote platelet integrin

Content Provider	Semantic Scholar
Author	Kasirer-Friede, Ana Kang, Jian Kahner, Bryan N. Ye, Feng Ginsberg, Mark H. Shattil, Sanford J.
Copyright Year	2014
Abstract	ADAP is an hematopoietic-restricted adapter protein that promotes integrin activation and is a carrier for other adapter proteins, SKAP1 and SKAP2. In T lymphocytes, SKAP1 is the ADAPassociated molecule that activates integrins through direct linkages with Rap1 effectors (RapL; RIAM). ADAP also promotes integrin αIIbβ3 activation in platelets, which lack SKAP1, suggesting an ADAP integrin-regulatory pathway different than in lymphocytes. Here we characterized a novel association between ADAP and two essential integrin β cytoplasmic tailbinding proteins involved in αIIbβ3 activation, talin and kindlin-3. GST pull-downs identified distinct regions in ADAP necessary for association with kindlin or talin. ADAP was physically proximal to talin and kindlin-3 in human platelets, as assessed biochemically, and by immunofluorescence microscopy and proximity ligation. Relative to wild-type mouse platelets, ADAP-deficient platelets exhibited reduced co-localization of talin with αIIbβ3, and reduced irreversible fibrinogen binding in response to a PAR4 thrombin receptor agonist. When ADAP was heterologously expressed in CHO cells co-expressing αIIbβ3, talin, PAR1 and kindlin-3, it associated with an αIIbβ3/talin complex and enabled kindlin-3 to promote agonist-dependent ligand binding to αIIbβ3. Thus, ADAP uniquely promotes activation of and irreversible fibrinogen binding to platelet αIIbβ3 through interactions with talin and kindlin-3. For personal use only. at UNIV KENTUCKY MED CTR on March 5, 2014. bloodjournal.hematologylibrary.org From
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://cvrc.med.uky.edu/sites/default/files/Blood-2014-Kasirer-Friede-blood-2013-08-520627.pdf
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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