MYPT1

MYPT1, or myosin phosphatase targeting subunit 1, is a protein encoded by the PPP1R12A gene in humans. It functions as a regulatory subunit of the heterotrimeric myosin light chain phosphatase (MLCP) complex, which dephosphorylates the regulatory light chain of myosin II (MLC20). The MLCP holoenzyme consists of a catalytic subunit (PP1C: PPP1CA, PPP1CB, or PPP1CC) and a regulatory subunit such as MYPT1, which targets the phosphatase to myosin filaments and enables site-specific dephosphorylation of MLC20. Through this targeting, MYPT1 plays a central role in controlling contractile activity and cytoskeletal dynamics in smooth muscle and non-muscle cells.

Regulation of MLCP activity is a key aspect of MYPT1 function. In smooth muscle, MLCK phosphorylates MLC20 to promote contraction, whereas MLCP dephosphorylates it to promote relaxation. The RhoA/ROCK signaling pathway inhibits MLCP by phosphorylating MYPT1 at specific residues, thereby sustaining contraction. Signaling via nitric oxide and the cGMP–PKG axis can counteract this inhibition, contributing to relaxation by promoting MLCP activity.

Structure and isoforms: The PPP1R12A gene produces multiple MYPT1 isoforms through alternative splicing, with tissue-specific expression patterns. The protein contains regions that bind PP1C and myosin II, targeting MLCP to contractile filaments.

Interactions and function: MYPT1 directly binds the catalytic PP1C subunits and recruits MLCP to myosin II, enabling dephosphorylation of MLC20. Its phosphorylation state, governed by kinases such as ROCK, modulates phosphatase activity and influences cell migration, cytokinesis, and contractility.

Clinical relevance: Altered MYPT1 signaling and MLCP regulation have been linked to vascular dysfunction and hypertension, reflecting changes in smooth muscle tone and contractility.

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