NDLI: Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo

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Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo

Content Provider	Scilit
Author	Bezman, Natalie A. Lian, Lurong Abrams, Charles S. Brass, Lawrence F. Kahn, Mark L. Koretzky, Gary A.
Copyright Year	2008
Description	Src homology 2 domain–containing leukocyte phosphoprotein of 76 kD (SLP76), an adaptor that plays a critical role in platelet activation in vitro, contains three N-terminal tyrosine residues that are essential for its function. We demonstrate that mice containing complementary tyrosine to phenylalanine mutations in Y145 (Y145F) and Y112 and Y128 (Y112/128F) differentially regulate integrin and collagen receptor signaling. We show that mutation of Y145 leads to severe impairment of glycoprotein VI (GPVI)–mediated responses while preserving outside-in integrin signaling. Platelets from Y112/128F mice, although having mild defects in GPVI signaling, exhibit defective actin reorganization after GPVI or αIIbβ3 engagement. The in vivo consequences of these signaling defects correlate with the mild protection from thrombosis seen in Y112/128F mice and the near complete protection observed in Y145F mice. Using genetic complementation, we further demonstrate that all three phosphorylatable tyrosines are required within the same SLP76 molecule to support platelet activation by GPVI.
Related Links	http://jem.rupress.org/content/205/8/1775.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525600/pdf
Ending Page	1788
Page Count	14
Starting Page	1775
DOI	10.1084/jem.20080240
Journal	The Journal of experimental medicine
Issue Number	8
Volume Number	205
Language	English
Publisher	Rockefeller University Press
Publisher Date	2008-07-28
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Function Signaling Platelet Defects Glycoprotein Gpvi Tyrosines Differentially Slp76 Y145 Journal: The Journal of experimental medicine (Vol- 205, Issue- 8)
Content Type	Text

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