Functional characteristics and research trends of PDE11A in human diseases (Review)

Abstract

cAMP and cGMP are important secondary messengers involved in cell regulation and metabolism driven by the G protein-coupled receptor. cAMP is converted via adenylyl cyclase (AC ) and activates protein kinase A to phosphorylate intracellular proteins that mediate specific responses. cAMP signaling serves a role at multiple steps in tumorigenesis. The level of cAMP is increased in association with cancer cell formation through activation of AC -stimulatory G protein by mutation. Phosphodiesterases (PDE s) hydrolyze cAMP and cGMP to AMP and GMP. PDE s are composed of 11 families, and each can hydrolyze cAMP and cGMP or both cAMP and cGMP. PDE s perform various roles depending on their location and expression site, and are involved in several diseases, including male erectile dysfunction, pulmonary hypertension, Alzheimer's disease and schizophrenia. PDE 11A is the 11th member of the PDE family and is characterized by four splice variants with varying tissue expression and N-terminal regulatory regions. Among tissues, the expression of PDE 11A was highest in the prostate, and it was also expressed in hepatic skeletal muscle, pituitary, pancreas and kidney. PDE 11A is the first PDE associated with an adrenocortical tumor associated genetic condition. In several studies, three PDE 11A mutations have been reported in patients with Cushing syndrome with primary pigmented nodular adrenocortical disease or isolated micronodular adrenocortical disease without other genetic defects. It has been reported that an increase in PDE 11A expression affects the proliferation of glioblastoma and worsens patient prognosis. The present mini-review summarizes the location of PDE 11A expression, the impact of structural differences and disease relevance.