Target intelligence / Profile preview

Protein phosphatase 1 regulatory inhibitor subunit 14A (PPP1R14A)

Target
PPP1R14A
Molecular classification
Protein phosphatase inhibitor, Regulatory protein, Signal transduction modulator
01

Overview

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].

Other names
CPI-17CPI17PPP1INLProtein phosphatase 1 regulatory subunit 14A17 kDa PKC-potentiated inhibitory protein of PP1PKC-potentiated inhibitory protein of PP117-KDa proteinprotein kinase C-potentiated inhibitor protein of 17 kDa
02

Mechanism of action

Phosphorylation-dependent inhibition of myosin light chain phosphatase (MLCP), leading to increased myosin phosphorylation and smooth muscle contraction

03

Biological functions

Inhibition of smooth muscle myosin phosphataseRegulation of smooth muscle contractionCa2+ sensitization of contractile apparatusSignal transductionModulation of neuronal synaptic depression
04

Disease associations

Cancer (including prostate and pancreatic cancer, head and neck squamous cell carcinoma)Cardiovascular disease (via regulation of smooth muscle tone and vascular contractility)Inflammatory disease (airway hyperresponsiveness, uterine contractility)Therapeutic resistance in cancerTumorigenesis
05

Safety considerations

Modulation of PPP1R14A may impact vascular, bronchial, or uterine tone, with risks of excessive contraction or relaxationOverexpression or dysregulation may contribute to tumorigenesis and therapeutic resistance in cancer[2]
06

Biomarkers

Candidate biomarker for certain cancers (e.g., prostate cancer, head and neck squamous cell carcinoma)[2]Potential marker of smooth muscle contractile status

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