Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase targeting subunit and inhibits myosin phosphatase activity

Abstract

Myotonic dystrophy protein kinase (DMPK) and Rho-kinase are related. An important function of Rho-kinase is to phosphorylate the myosin-binding subunit of myosin phosphatase (MYPT1) and inhibit phosphatase activity. Experiments were carried out to determine if DMPK could function similarly. MYPT1 was phosphorylated by DMPK. The phosphorylation site(s) was in the C-terminal part of the molecule. DMPK was not inhibited by the Rho-kinase inhibitors, Y-27632 and HA-1077. Several approaches were taken to determine that a major site of phosphorylation was T654. Phosphorylation at T654 inhibited phosphatase activity. Thus both DMPK and Rhokinase may regulate myosin II phosphorylation. ß

Phosphorylation of Myosin Phosphatase Targeting Subunit 3 (MYPT3) and Regulation of Protein Phosphatase 1 by Protein Kinase A

“…As MYPT1 has been shown to be phosphorylation targets for a variety of protein kinases (12,13,15,17,18), it remains to be seen if MYPT3 can also be phosphorylated by kinases other than PKA. On the other hand, PKA has been reported to interfere with actomyosin cytoskeleton rearrangements through a number of signaling pathways (37,38).…”

“…There are several putative phosphorylation sites on these isoforms of the MYPT family, and some had been shown to be phosphorylated and regulated by a range of kinases, including Rho kinase (ROK/ROCK), myotonic dystrophy-related CDC42-binding kinase (MRCK), myotonic dystrophy protein kinase, Raf-1, and integrin-linked kinase (12,(15)(16)(17)(18)(19). Phosphorylation of a threonine in MYPT1 (Thr-696) and MBS85 (Thr-560) in a highly conserved motif resulted in inhibition of PP1c activity toward p-RMLC.…”

Identification and Characterization of Zipper-interacting Protein Kinase as the Unique Vascular Smooth Muscle Myosin Phosphatase-associated Kinase

“…Biochemical isolation of SMPP-1M has lead to the recovery of SMPP-1M-associated kinase activity (15)(16)(17)(18)(19). The SMPP-1M-associated kinase phosphorylates the myosin binding subunit (MBS) of SMPP-1M and inhibits SMPP-1M activity.…”

Myosin Phosphatase-Rho Interacting Protein

“…Several downstream signaling pathways that inhibit myosin phosphatase activity have been discovered recently, including RhoA/Rho kinase (21), protein kinase C activation of the inhibitory phosphoprotein CPI-17 (22), and arachidonic acid (23,24). In addition, several kinases copurify with myosin phosphatase, including ZIP-like kinase (25), integrin-linked kinase (26), myotonic dystrophy-related kinase (27), and Raf-1 (28), each of which can phosphorylate MBS and inhibit myosin phosphatase activity. RhoA/Rho kinase has been the most extensively studied myosin phosphatase inhibitor.…”