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

• Published in: FEBS letters Vol. 493; no. 2; pp. 80 - 84
• Main Authors: Murányi, Andrea, Zhang, Rongxin, Liu, Feizhou, Hirano, Katsuya, Ito, Masaaki, Epstein, Henry F., Hartshorne, David J.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 30.03.2001
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Amides - pharmacology; Animals; Base Sequence; Binding Sites; DMPK, myotonic dystrophy protein kinase; DNA Primers - genetics; Enzyme Inhibitors - pharmacology; GST, glutathione S-transferase; Humans; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; MDFPK, myotonic dystrophy family of protein kinases; MP, myosin phosphatase; Myosin phosphatase; Myosin target subunit; Myosin-Light-Chain Phosphatase; Myotonic Dystrophy - enzymology; Myotonic dystrophy protein kinase; Myotonin-Protein Kinase; MYPT, myosin phosphatase target subunit; Phosphoprotein Phosphatases - antagonists & inhibitors; Phosphoprotein Phosphatases - chemistry; Phosphoprotein Phosphatases - metabolism; Phosphorylation; PP1cδ, delta isoform of the catalytic subunit of protein phosphatase type 1; Protein Subunits; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Pyridines - pharmacology; Recombinant Proteins - metabolism; rho-Associated Kinases; Rho-kinase; Rho-kinase, Rho-associated protein kinase (ROK, ROCK, p160ROCK); Space life sciences; MP, myosin phosphatase; Myotonic dystrophy protein kinase; GST, glutathione S-transferase; Myosin target subunit; MYPT, myosin phosphatase target subunit; Rho-kinase; Rho-kinase, Rho-associated protein kinase (ROK, ROCK, p160 ROCK); Myosin phosphatase; MDFPK, myotonic dystrophy family of protein kinases; PP1cδ, delta isoform of the catalytic subunit of protein phosphatase type 1; DMPK, myotonic dystrophy protein kinase; Non-programmatic
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(01)02283-9

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 Rho-kinase may regulate myosin II phosphorylation.