Phosphatidylinositol-dependent kinase

This is still poorly understood. Proteins that bind to PI(3,4)P2 or Pl(3,4,5)Pj have PH domains (pleckstrin homology domains). One example of such a protein is protein kinase B PKB) this is activated by phosphorylation that is catalyzed by another PH domain kinase, PDKl (phosphatidylinositol-dependent kinase). Activated PKB phosphorylates a ribosomal protein, protein S6, which leads to increased rates of translation of selected mRNA molecules. 

Kim JH, Na HJ, Kim CK, Kim JY, Ha KS, Lee H, Chung HT, Kwon HJ, Kwon YG and Kim YM. 2008. The non-provitamin A carotenoid, lutein, inhibits NF-KB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-KB-inducing kinase pathways role of H2O2 in NF-kB activation. Free Radic Biol Med 45(6) 885-896. 

Knox KA, Gordon J (1994) Protein tyrosine kinases couple the surface immunoglobulin of germinal center B cells to phosphatidylinositol-dependent and -independent pathways of rescue from apoptosis. Cell Immunol 155 62-76... 

Ataxia telangiectasia is an autosomal recessive disease characterized by neurologic, endocrine, and hepatic abnormalities, as well as a predisposition to malignancy (119). The defect has been traced to a gene on chromosome 11, the ATM gene that codes for a phosphatidylinositol 3-kinase-like protein which is related to the catalytic subunit of DNA-dependent protein kinase. This protein has a role in signal transduction, DNA repair, and control of the cell cycle (120). Affected patients have a defect in cell-mediated immunity. A decrease in semm IgA is seen in a majority of affected patients. IgG2 or total IgG and IgE levels may be decreased, with an increase in IgM. Patients are susceptible to chronic respiratory... 

Hartley, K. O., Gell, D., Smith, G. C., et al., DNA-dependent protein kinase catalytic subunit A relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell 82, 849-856 (1995). 

Dadi, H. Ke, S. Roifman, C.M. Activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 receptor is dependent on protein tyrosine kinase activity. Blood, 84, 1579-1586 (1994)... 

Khan, F.A. Goforth, P.B. Zhang, M. Satin, L.S. Insulin activates ATP-sen-sitive K channels in pancreatic b-cells through a phosphatidylinositol 3-kinase-dependent pathway. Diabetes, 50, 2192-2198 (2001)... 

Minshall, C. Arkins, S. Freund, G.G. Kelley, K.W. Requirement for phosphatidylinositol 3 -kinase to protect hemopoietic progenitors against apoptosis depend.s upon the extracellular survival factor. J. Immunol., 156, 939-947 (1996)... 

Welters, R Takegawa, K. Emr, S.D. Chrispeels, M.J. AtVPS34, a phosphatidylinositol 3-kinase of Arabidopsis thaliana, is an essential protein with homology to a calcium-dependent lipid binding domain. Proc. Natl. Acad. Sci. USA, 91, 11398-11402 (1994)... 

One of the most important effects of insulin is to increase glucose uptake by cells 373/389 The mechanism is thought to depend upon the transporter protein GLUT4, which is stored within the membranes of small cytoplasmic vesicles. Binding of insulin to its receptors induces movement of these vesicles to the plasma membrane where fusion with the plasma membrane makes the GLUT4 molecules available for glucose transport.390 Phosphatidylinositol 3-kinase also plays an important role. The PtdIns(3,4)P2 and PtdIns(3,4,5)P3 generated by this enzyme (Fig. 11-9)... 

Glutamate-mediated Ca2+ entry through NMDA at the plasma membrane level and mobilization of Ca2+from intracellular stores through PLC-mediated generation of PtdIns-3/J is indispensable for the basal NF-kB activity. Three cytosolic Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p2 l(ras)/phosphatidylinositol 3-kinase (Ptdlns-3K)/Akt pathways, are simultaneously involved in the steps linking the Ca2+ to NF-kB activity (Lilienbaum and Israel, 2003 Marchetti et al., 2004 Lubin et al., 2005). Calmodulin modulates calcineurin, a Ca2+-dependent protein phosphatase, which plays a role in the basal NF-kB activity, whilst stimulation of both the calmodulin kinase II and Akt kinase pathways results in the up-regulation of the transcriptional potential of the p65 subunit of NF-/cB (Lilienbaum and Israel,... 

In primary cultures of neonatal cerebellar granule neurons, all Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p21(ras)/phosphatidylinositol 3 -kinase (Ptdlns-3K)/Akt pathway, converge towards NF-kB at the levels of nuclear translocation as well as transcription. The duration of NF-kB activation is a critical determinant for sensitivity toward excitotoxic stress and is dependent on the different upstream and downstream signaling associated with various kinases. This is in contrast to studies in non-neuronal cells, which either do not respond to Ca2+ or do not simultaneously activate all three cascades (Lilienbaum and Israel, 2003). Collective evidence suggests that brain inflammatory processes differ from systemic inflammation not only in the involvement of various types of neural cells but also in differences in response to second messengers. 

Marchetti L., Klein M., Schlett K., Pfizenmaier K., and Eisel U. L. M. (2004). Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-metliyl-D-aspartate receptor activation-Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kB pathway. J. Biol. Chem. 279 32869-32881. 

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