Clustering of Integrin alphaIIb beta3 complexes

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.<br>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.

纤维蛋白原结合的整合素αIIbβ3簇将血小板聚集形成血小板栓，并产生细胞内信号（由外向内），导致进一步的血小板活化和血小板栓收缩。细胞内的整合素αIIbβ3簇将结合于整合素β3链的SRCs拉近。SRC与整合素αIIbβ3构成固有联系。在未受刺激的细胞中，此SRC处于非活性状态，通过磷酸化Y530与SH2结构域之间的内部相互作用实现自抑制。CSK对Y530残基具有选择性，并阻止PTP1B（一种能够去磷酸化Y530的蛋白酪氨酸磷酸酶）对SRC的接近。