The PPP1R14A gene is located on chromosome 19 in humans and chromosome 7 in mice . The protein consists of 147 amino acids and shares about 90% sequence identity with its porcine counterpart . The gene is expressed in various tissues, including the coronary arteries, aorta, and smooth muscle tissues .
PPP1R14A acts as a phosphorylation-dependent inhibitor of smooth muscle myosin phosphatase . When phosphorylated at the Thr-38 residue, it undergoes a conformational change that significantly increases its inhibitory activity . This inhibition leads to increased myosin phosphorylation and enhanced smooth muscle contraction, a phenomenon known as Ca²⁺ sensitization .
Multiple kinases, such as PKC, ROCK, PKN, ZIPK, ILK, and PAK, can phosphorylate PPP1R14A . Agonist stimulation of smooth muscle primarily enhances PPP1R14A phosphorylation through PKC and ROCK . In addition to its role in smooth muscle, PPP1R14A is also involved in long-term synaptic depression in Purkinje neurons .
PPP1R14A has been implicated in various diseases and conditions. It is up-regulated in some cancer cells, leading to hyperphosphorylation of tumor suppressor merlin/NF2 . In prostate cancer, PPP1R14A expression is associated with increased cell proliferation and certain genetic risk factors . Additionally, PPP1R14A has been linked to conditions such as Israeli Tick Typhus and Compensatory Emphysema .
Research on PPP1R14A continues to uncover its roles in cellular processes and disease mechanisms. The protein’s ability to regulate smooth muscle contraction and its involvement in cancer make it a potential target for therapeutic interventions. Antibodies against PPP1R14A, such as mouse anti-human PPP1R14A, are used in research to study its expression and function in various tissues .