Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase)

TLDR

Rho GTPase regulates smooth‑muscle contraction and actin–myosin interactions by activating Rho‑kinase, which phosphorylates the myosin‑binding subunit of myosin phosphatase and thereby reduces its activity. In NIH 3T3 cells, overexpression of RhoA or constitutively active RhoA increased phosphorylation of the myosin‑binding subunit and myosin light chain, confirming that Rho inhibits myosin phosphatase through Rho‑kinase.

Abstract

The small guanosine triphosphatase Rho is implicated in myosin light chain (MLC) phosphorylation, which results in contraction of smooth muscle and interaction of actin and myosin in nonmuscle cells. The guanosine triphosphate (GTP)-bound, active form of RhoA (GTP⋅RhoA) specifically interacted with the myosin-binding subunit (MBS) of myosin phosphatase, which regulates the extent of phosphorylation of MLC. Rho-associated kinase (Rho-kinase), which is activated by GTP⋅RhoA, phosphorylated MBS and consequently inactivated myosin phosphatase. Overexpression of RhoA or activated RhoA in NIH 3T3 cells increased phosphorylation of MBS and MLC. Thus, Rho appears to inhibit myosin phosphatase through the action of Rho-kinase.