Myosin phosphatase target subunit: Many roles in cell function

Abstract

Phosphorylation of myosin II is important in many aspects of cell function and involves a myosin kinase, e.g. myosin light chain kinase, and a myosin phosphatase (MP). MP is regulated by the myosin phosphatase target subunit (MYPT1). The domain structure, properties, and genetic analyses of MYPT1 and its isoforms are outlined. MYPT1 binds the catalytic subunit of type 1 phosphatase, δ isoform, and also acts as an interactive platform for many other proteins. A key reaction for MP is with phosphorylated myosin II and the first process shown to be regulated by MP was contractile activity of smooth muscle. In cell division and cell migration myosin II phosphorylation also plays a critical role and these are discussed. However, based on the wide range of partners for MYPT1 it is likely that MP is implicated with substrates other than myosin II. Open questions are whether the diverse functions of MP reflect different cellular locations and/or specific roles for the MYPT1 isoforms.

Myosin Phosphatase Target Subunit 1 (MYPT1) Regulates the Contraction and Relaxation of Vascular Smooth Muscle and Maintains Blood Pressure

“…As a focal point for smooth muscle contractile signaling, RLC phosphorylation is regulated by multiple pathways involving MLCK activity regulated by Ca 2ϩ /calmodulin and phosphorylation (10). MLCP activity is regulated by MYPT1 and CPI-17 phosphorylation (11,14,15,25). Interacting temporal and spatial signaling responses basically control the ratio of MLCK to MLCP activities, thereby physiologically fine-tuning the extent of RLC phosphorylation and arterial tone.…”

“…MLCP is a heterotrimer that consists of a catalytic type 1 phosphatase subunit (PP1c␦), a regulatory subunit, MYPT1, and a 20-KDa subunit (M20) with unknown function (14,15). MYPT1 enhances the catalytic activity and specificity of PP1c␦ toward phosphorylated RLC in its binding to myosin (16).…”

“…Finally, MYPT1 acts as a scaffold for other proteins including Par-4, HSP27, and M-RIP (25). Thus, MYPT1 appears to play a central role in regulating MLCP activity through direct interactions with PP1c␦, its phosphorylation by different kinases, and its actions as a scaffold for other proteins that may affect RLC phosphorylation (8,11,14,25).…”

O-Linked β-N-Acetylglucosaminyltransferase Substrate Specificity Is Regulated by Myosin Phosphatase Targeting and Other Interacting Proteins

“…MYPT1 is a known targeting regulatory subunit of PP1␤ (also known as PP1␦) (for a review, see Ref. 26), whereas CARM1 is a known transcriptional coactivating arginine methyltransferase (for a review, see Ref. 27).…”

Rho-kinase Contributes to Sustained RhoA Activation through Phosphorylation of p190A RhoGAP

“…RhoA regulates these functions through its specific effectors such as Rho-kinase/ROCK/ROK and mDia (2). We previously found that Rho-kinase phosphorylates myosin phosphatase target protein 1 (MYPT1) 3 of myosin phosphatase and thereby inactivates its phosphatase activity, resulting in an increase in the phosphorylation of myosin light chain followed by smooth muscle contraction (3)(4)(5). Rho-kinase increases the agonistinduced Ca 2ϩ sensitivity and contributes to sustained contraction of smooth muscle (6).…”