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We previously reported that depolarization of the vascular smooth muscle plasma membrane activates the Ca 2+ -dependent proline-rich tyrosine kinase 2 (Pyk2) upstream of the RhoA/Rho-associated kinase (ROCK) pathway leading to phosphorylation of MYPT1 (the myosin-targeting subunit of myosin light chain phosphatase) and the 20 kDa light chain of myosin (LC 20 ).The resulting sustained elevation of LC 20 phosphorylation then accounts for the tonic contractile response to membrane depolarization.However, the mechanism whereby Pyk2 activates RhoA remains unclear.It is conceivable that Rho guanine nucleotide exchange factors (RhoGEFs) may connect activated Pyk2 to RhoA activation via phosphorylation and activation of its RhoGEF activity.In this study, we investigated activation of RhoA and RhoGEFs in membrane depolarization-induced contraction of rat caudal arterial smooth muscle.Rhosin (10 -30 μM), a RhoA inhibitor, concentration-dependently inhibited both the phasic and tonic components of the 60 mM K + -induced contractile response of arterial strips.This inhibitory effect of Rhosin was particularly prominent in the tonic component of contraction.On the other hand, Y16 ( 1 -30 μM), a RhoGEF inhibitor, had little inhibitory Posted on 1 Sep
Aida et al. (Sun,) studied this question.