The fibrinogen-bound integrin alphaIIb beta3 clusters platelets together to form a platelet plug and generates intracellular signals (outside-in) causing further platelet activation and platelet plug retraction.Intracellular integrin alphaIIb beta3 clustering brings SRCs bound to integrin beta3 chains into proximity. SRC associates constitutively with integrin alphaIIb beta3. In unstimulated cells this SRC is inactive, auto-inhibited by an internal interaction between phosphorylated Y530 and the SH2 domain. CSK is selective for the Y530 residue and prevents access to SRC of PTP1B, a protein tyrosine phosphatase that is capable of de-phosphorylating Y530.
DeGrado, WF, Li, R, Bennett, JS
Shattil, SJ
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