PDEδ was originally identified as a fourth subunit of rod-specific cGMP PDE. PDEδ is thought to be a specific soluble transport factor for certain prenylated (farnesyl) proteins and Arl2-GTP, a regulator of PDE-mediated transport. PDEδ sustains the spatial organization of KRAS by facilitating its diffusion in the cytoplasm. Conversely, PDEδ down-modulation randomizes RAS distributions to all membranes in the cell and suppresses regulated signaling through wild-type RAS and also constitutive oncogenic RAS signaling in cancer cells[1],[2].

Phosphodiesterases (PDE; EC 3.1.4.-) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Roughly, the sub-types can be divided into 3 groups: one group of enzymes specifically degrades cyclic adenosine monophosphate (cAMP; PDE4, 7 and 8), another group specifically targets cyclic guanosine monophosphate (cGMP; PDE5, 6, and 9), whereas the third group of enzymes (including PDE1, 2, 3, 10, and 11) are non specific towards either cAMP or cGMP[3]. PDEs influence a vast array of pharmacological processes, including pro-inflammatory mediator production and action, ion channel function, muscle contraction, learning, differentiation, apoptosis, lipogenesis, glycogenolysis and gluconeogenesis. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia[4].

Phosphodiesterases listed: PDE, PLC, PLD