Implications of Phosphoinositide 3-Kinase (PI3K) Signalling in Cellular and Molecular Mechanisms of Respiratory Diseases

Phosphoinositide 3-kinases (PI3Ks) are the central modulators of different cellular signalling pathways and play an important role in cell survival, proliferation, growth, metabolism, cell polarity, and activation of various immune cells, to mention a few. PI3Ks are classified into three main categories based on their structure and substrate specificity. In mammals and higher eukaryotes, there exist four isoforms of class I PI3K (PI3Kα, β, γ, δ), three isoforms of class II PI3K (PI3KC2α, C2β, C2γ), and a single class III PI3K. These isoforms have overlapping functions, but the stimulation for specific receptors required for their activation is also different. PI3Ks regulate a plethora of signalling cascades that are involved in pathway members which are involved in various physiological processes such as ROS generation, mast cell activation, neutrophil migration, etc. These events eventually lead to inflammation in various respiratory diseases like chronic obstructive pulmonary disease, asthma, emphysema, cystic fibrosis, etc. PI3K signalling has also been reported to be involved in SARS-CoV-2-mediated pneumonia in the lungs. Nowadays, inhibition of various members of PI3K pathway is the leading approach for the treatment of respiratory diseases.