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Protein phosphatase 1 regulatory inhibitor subunit 14A (PPP1R14A), also called CPI-17, is a phosphorylation-dependent inhibitor of smooth muscle myosin phosphatase, especially the catalytic subunit PPP1CA[1][3][7]. When phosphorylated, particularly at Thr-38, it potently suppresses myosin light chain phosphatase activity, increasing myosin phosphorylation and promoting smooth muscle contraction independent of intracellular Ca2+ levels—a process called Ca2+ sensitization[1][2]. Multiple kinases, including protein kinase C (PKC) and Rho-associated kinase (ROCK), phosphorylate PPP1R14A, regulating contraction in vascular, bronchial, and uterine smooth muscle. Beyond muscle, PPP1R14A is implicated in synaptic function and long-term synaptic depression in neurons[1]. Aberrant expression is associated with cancer development, resistance to immunotherapy, and increased cell proliferation in several tumor types, making it a promising therapeutic target and biomarker candidate[2].
Phosphorylation-dependent inhibition of myosin light chain phosphatase (MLCP), leading to increased myosin phosphorylation and smooth muscle contraction
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