Investigating the isoform-specific role of phosphoinositide 3- kinase p110delta

摘要: Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes that regulate diverse array biological functions in every cell type by generating lipid second messengers. The PI3K is comprised multiple isoforms divided into three main classes; class I, II and III. All I PI3Ks heterodimers consisting ~110 kDa catalytic subunit associated with regulatory subunit. Class further subdivided IA and class IB, which activated downstream tyrosine kinases or G protein-coupled receptors, respectively. mammalian subunits p110α, p110β p110δ. involved cellular processes, deregulation signalling pathways have been linked to number diseases such as cancer, inflammation immunity diabetes. Targeting itself effectors an approach has the potential be huge therapeutic benefit, however, also important normal homeostasis inhibition all non-selective inhibitors toxic cell. To enable individual targeted therapeutically, it first understand specific mediated each isoforms. This work focuses on addressing isoform-specific role Unlike p110α p110β, p110δ more restricted tissue distribution most abundantly expressed leukocytes. However, there instances where cells non-haematopoietic origin high levels expression, breast cells, melanocytes microglia. Using cell-based models explore signalling, our revealed coupling kinase receptor, c-kit, appears remain largely unaltered primary leukocytes stably express transforming polyoma middle T antigen. Stable overexpression non-leukocyte line, NIH 3T3, results downregulation p110β expression a striking impact morphology. Finally, we identified gene promoter region mediates leukocyte-specific expression.