Fig 7. Agonist-induced dissociation of the SPL/RGS/SHP-1 complex and formation of the SPL/PP1 complex.

In resting platelets spinophilin is phosphorylated on Y398 and Y483 and bound to either RGS10 or RGS18. Platelet activation by agonists for thrombin or TxA₂ receptors activates SHP-1 by causing phosphorylation of SHP-1(Y536). This triggers dissociation of the SPL/RGS/SHP-1 complex, allowing RGS10 and RGS18 to inhibit signaling. Dissociation of SHP-1 from spinophilin is followed by binding of PP1. Binding to spinophilin inhibits the phosphatase, promoting phosphorylation of PP1 substrates such as myosin light chain (MLC).