TI - Chloride conductance is required for the protein kinase A and Rac1 -dependent phosphorylation of moesin at Thr-558 by KCl in PC12 cells . AB - Moesin is a member of the ERM family , a family of cross-linkers between the plasma membrane and the actin cytoskeleton , which are known to be activated by phosphorylation . Previously , we reported the RhoA and Rho kinase -dependent phosphorylation of moesin at Thr-558 in hippocampal neuronal cells by glutamate . Here we studied the induction of moesin phosphorylation by KCl ( 60 mm ) in PC12 cells . Moesin phosphorylation at Thr-558 was increased after 2 min of KCl treatment , peaked at 5 min , and returned to the basal level by 60 min . KCl also activated Rac1 , but not RhoA , in PC12 cells , and KCl -induced moesin phosphorylation was suppressed in dominant negative Rac1 ( N17 Rac1 ) -expressed cells . The inhibition of protein kinase A ( PKA ) , known as an upstream kinase of Rac1 , abolished Rac1 activation and moesin phosphorylation by KCl . Interestingly , the phosphorylation of moesin by KCl was independent of KCl -induced membrane depolarization and calcium influx but was dependent on KCl -induced chloride conductance. 60 mm KCl induced chloride conductance in PC12 cells , and pretreatment with Cl - channel blocker abolished Rac1 activation and moesin phosphorylation by KCl . These results suggest that the phosphorylation of moesin at Thr-558 in PC12 cells by KCl treatment is PKA - and Rac1 -dependent and that KCl -induced chloride conductance is involved in the activation of this signaling system .