The A-kinase anchoring protein 12 (AKAP12) belongs to a family of scaffold proteins, which anchor signaling proteins such as PKA in a spatiotemporal manner⁴. AKAPs generally bind PKA at their N-terminus, while the sequence at their C-terminus determines their spatial location⁴. To date, more than 50 AKAPs have been identified and perceived to integrate signaling pathways by anchoring multi-protein complexes¹.

AKAP12 integrates diverse signaling pathways such as PKA, PKC, and β₂-adrenergic receptor^7,8. Similar to other members of this protein-family, AKAP12 contains a PKA binding domain. In addition, AKAP12 also contains a docking site for PKC^2,6 and a myristoyl acid that sequesters it to the plasma membrane⁷.

AKAP12 is widely expressed in a variety of tissues with the highest expression in male and female reproductive organs, skeletal muscle, kidneys, and urinary tract⁵.

One of the most characterized activities of AKAP12 is regulation of the cell cycle³. AKAP12 controls two fundamental cell processes such as the G1/S transition and cytokinesis. In that being said, studies in NIH-3T3 fibroblasts, showed that ectopic expression of AKAP12 reduced cyclin D1 levels and the phosphorylation of its downstream target Rb, and consequently attenuated cell-cycle progression³. Furthermore, in HeLa cells, knockdown of AKAP12 resulted in profound changes in cell morphology, which indicates the inability of cells to divide³.

Given that AKAP12 plays a pivotal role in cell cycle regulation, it is not surprising that in some cases it is involved in cancer malignancies. It is now clear that AKAP12 is a key driver of gastrointestinal cancers such as colorectal cancer and hepatocellular carcinomas⁸.