Figure 1

The Ca²⁺ mobilization and DMR signals mediated through endogenous PARs in A431. (a) The endogenous PARs and their corresponding agonists. Both receptors mediate G_q signaling, which proceeds through activation of the receptor, its coupled G protein and downstream target phospholipase C (PLC). The PLC hydrolyzes the membrane lipid phosphatidylinositol bisphosphate (PIP₂), producing inositol triphosphate (IP₃) and diacylglycerol (DAG). IP₃ binds to and opens a calcium channel in the endoplasmic reticulum, leading to calcium mobilization. Calcium alters many cellular processes. The interaction of both DAG and calcium with protein kinase C (PKC) activates PKC kinase activity, which, in turn, phosphorylates many different protein targets including small GTPase Rho, leading to the remodeling of cytoskeletal structure. (b) The increase in intracellular Ca²⁺ level as a function of the concentration of different soluble PAR agonists. (c) The real-time dynamic mass redistribution signals induced by SFLLR-amide at different doses. The solid arrow indicates the time when SFLLR-amide is introduced. The DMR consists of two phases: an increase signal (termed Positive-DMR, P-DMR) and a sequential decay signal (termed Negative-DMR, N-DMR). (d) The amplitudes of both P-DMR and N-DMR events, calculated as indicated in (c), as a function of SFLLR-amide concentration.