Figure 1

Platelet aggregation requires contraction, adhesion and secretion. ROK promotes platelet aggregation independent of MLCP inhibition. Platelet contraction requires Ser19 myosin light chain (MLC₂₀) phosphorylation by Ca²⁺:calmodulin (CaM)-dependent myosin light chain kinase (MLCK). Agonists such as arachidonic acid initiate platelet contraction by augmenting [Ca²⁺]_cyt derived from both the extracellular fluid via transient receptor potential (TRP) channels and intracellular dense tubular system stores. Contraction is opposed when MLC₂₀ is dephosphorylated by myosin light chain phosphatase (MLCP). It is proposed that MLCP is regulated by two mechanisms: (i) G protein-coupled receptors (GPCRs) bearing the Gα₁₃ subunit activate membrane-bound RhoA, which activates Rho kinase (ROK) [23]; ROK is thought to inhibit MLCP by phosphorylating Thr855 on MYPT, the regulatory subunit of MLCP [24-26] (dashed line). (ii) PKC-dependent CPI-17 directly inhibits MLCP [24,27-29] (not shown). By inhibiting MLCP, both ROK and CPI-17 favour contraction independent of the prevailing [Ca²⁺]. Other than disinhibiting MLCP, there are other mechanisms by which ROK inhibition might oppose platelet aggregation: ROK is also involved in vesicle trafficking and degranulation, pseudopodium formation, stabilisation of platelet-fibrin binding and actin polymerisation.