Phosphatidylinositol-4,5-bisphosphate 3-kinase family: Introduction

PI3Ks are heterodimers composed of catalytic and regulatory subunits [3]. Catalytic subunit activity is tightly controlled by the associated regulatory subunits. PI3K activation is one of the most important signal transduction pathways used to transmit signals from cell-surface receptors to regulate intracellular processes (cell growth, survival, proliferation and movement). Receptors for growth factors, hormones, antigens and inflammatory stimuli all utilise this pathway [2]. PI3K catalytic and regulatory subunits play vital roles in normal cell function and in disease. Defects in PI3K signalling, via the PI3Kα oncogene for example, correlate with the development and maintenance of various human cancers. Experimental investigations using PI3K isoform-selective inhibitors has elucidated the roles of specific PI3K isoforms in whole-animal physiology and pathology. For example, PI3Kα is important in growth and metabolic regulation, PI3Kβ in thrombosis, and PI3Kδ and PI3Kγ are involved in inflammation and asthma. As PI3Kδ and PI3Kγ are the isoforms preferentially expressed in immune cells, δ/γ isozyme selective inhibitors are being considered for inflammatory and autoimmune diseases, as well as for malignancies. Progress made in developing PI3K-targeted agents as potential therapeutics for treating cancer and other diseases is reviewed by Fruman et al. (2017) [1].


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1. Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. (2017) The PI3K Pathway in Human Disease. Cell, 170 (4): 605-635. [PMID:28802037]

2. Hawkins PT, Anderson KE, Davidson K, Stephens LR. (2006) Signalling through Class I PI3Ks in mammalian cells. Biochem Soc Trans, 34 (Pt 5): 647-62. [PMID:17052169]

3. Vadas O, Burke JE, Zhang X, Berndt A, Williams RL. (2011) Structural basis for activation and inhibition of class I phosphoinositide 3-kinases. Sci Signal, 4 (195): re2. [PMID:22009150]

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