NOVEL FUNCTIONS OF PHOSPHATIDYLINOSITOL 3-KINASE IN TERMINALLY DIFFERENTIATED CELLS

Importance of phosphatidylinositol 3-kinase (PI 3-kinase) in signalling pathways leading to growth stimulation has already been reviewed in this journal and others. Evidence has now been accumulating that PI 3-kinase is involved in transmission of activation signals in terminally differentiated cells, especially signals starting from receptors which have no intrinsic tyrosine kinase domain. The pioneer works showed the presence of PI 3-kinase activity and the accumulation of the reaction products of PI 3-kinase correlated with the cell responses. However, these studies were done in only limited cell responses such as respiratory burst in neutrophils and degranulation in platelets. Recent finding of a potent and selective inhibitor of PI 3-kinase, wortmannin, reported from three independent groups including us, gave a new and powerful tool not only to confirm the suggested functions but also to reveal new functions of PI 3-kinase such as histamine release from antigen-stimulated mast cells/basophils and glucose uptake in insulin-stimulated adipocytes. Nearly one hundred papers which describe the action of wortmannin on various cells have been reported during one year after the publication of the discovery of wortmannin as PI 3-kinase inhibitor, suggesting possible involvement of the enzyme in the diverse cell responses besides cell proliferation.