Structural and functional diversity of phosphoinositide 3-kinases

Abstract

Phosphoinositide 3-kinases (PI3-kinases) have been shown to be recruited to cell surface receptor signal complexes whose formation is triggered by growth factors, cytokines and other ligands. PI3-kinases are also involved in protein sorting phenomena. A number of PI3-kinase isotypes have been characterised in several laboratories. Here the relations between the PI3-kinases, PI4-kinases and PI5-kinases and other potential phosphoinositide kinases are analysed. A study of the relation of structure to function for sequence motifs defined through the use of homology searches and protein modelling techniques is described and used to assign the family of phosphoinositide kinases to subgroups.

Insulin occludes leptin activation of ATP‐sensitive K+ channels in rat CRI‐G1 insulin secreting cells

“…This may be due to stimulation of different isoforms of PI 3_kinase (Zvelebil et al 1996) by leptin and insulin, respectively. Consequently, distinct but interacting cellular signalling pathways may be activated by these agents.…”

The Catalytic Subunit of Phosphoinositide 3-Kinase: Requirements for Oncogenicity

“…P110 can bind to p85 and is controlled by p85. These lipid kinases affect many biological functions such as cell proliferation, differentiation, apoptosis, and glucose transport (1)(2)(3)(4)(5)(6)(7)(8). A possible role of PI 3-kinases in oncogenic transformation was first suggested by the observation that PI 3-kinase activity was associated, via the regulatory subunit p85, with oncogene products such as polyoma middle T antigen (9,10) or v-Src (11,12).…”

Inhibition of Calcium-independent Mannose 6-Phosphate Receptor Incorporation into trans-Golgi Network-derived Clathrin-coated Vesicles by Wortmannin

“…Phosphoinositide 3-kinases (PI3Ks) have also been extensively studied for their role in cellular proliferation and differentiation resulting from their interaction with growth factor receptors (1). More recently, different types of PI3K have been isolated and cloned, which may play other roles in the cell, including the regulation of membrane traffic (2). Together with separate observations linking the small GTPase ADP-ribosylation factor, which is involved in budding of coated vesicles, to activation of phospholipase D, these studies have promoted widespread interest in the role of lipids in governing aspects of membrane traffic (3).…”

“…The first class includes the wortmannin-sensitive heterodimeric mammalian PI3Ks represented by the p85/p110 kinases, which link to receptors with tyrosine kinase activity (1), and the p101/p117 or p101/p120 PI3Ks, which are activated by heterotrimeric G-protein ␤␥-subunits (16). These heterodimeric PI3Ks exhibit an in vivo substrate preference for PIP 2 (17). The second class, specific for phosphatidylinositol (PtdIns), is exemplified by the wortmannin-resistant Vps34p from Saccharomyces cerevisiae (18) and a recently identified wortmannin-sensitive mammalian PtdIns 3-kinase (19).…”