scholarly journals Specific binding of the Akt-1 protein kinase to phosphatidylinositol 3,4,5-trisphosphate without subsequent activation

1996 ◽  
Vol 315 (3) ◽  
pp. 709-713 ◽  
Author(s):  
Stephen R. JAMES ◽  
C. Peter DOWNES ◽  
Roy GIGG ◽  
Simon J. A. GROVE ◽  
Andrew B. HOLMES ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Surface Plasmon Resonance ◽  
Protein Kinase ◽  
Association Constant ◽  
Kinase Activity ◽  
Specific Binding ◽  
Protein Kinase Activity ◽  
L6 Myotubes ◽  
Subsequent Activation ◽  
Phosphoinositide 3 Kinase

Recent evidence has suggested that activation of phosphoinositide 3-kinase (PI 3-kinase) is required for the activation of Akt-1 by growth factors and insulin. Here we demonstrate by two independent methods that Akt-1 from L6 myotubes binds to PtdIns(3,4,5)P3, PtdIns(3,4)P2 and PtdIns(4,5)P2 when presented against a background of phosphatidylserine (PtdSer) or a 1:1 mixture of PtdSer and phosphatidylcholine (PtdCho). No binding was observed with the lipids PtdIns(3,5)P2, PtdIns4P and PtdIns3P or background lipids. Activated, hyperphosphorylated forms of Akt-1 from insulin-stimulated L6 myotubes bound to PtdIns(3,4,5)P3 in a similar manner as inactive Akt-1. Quantitative analysis using surface plasmon resonance showed that the equilibrium association constant for the binding of Akt-1 to PtdIns(3,4,5)P3 was submicromolar and that PtdIns(3,4)P2 and PtdIns(4,5)P2 bound to Akt-1 with 3- and 6-fold lower affinities respectively. Interaction of Akt-1 with PtdIns(3,4,5)P3 did not activate the protein kinase activity, either before or after incubation with MgATP. A model is presented in which PtdIns(3,4,5)P3 may prime Akt-1 for activation by another protein kinase, perhaps by recruiting it to the plasma membrane.

PROTEIN KINASE ACTIVITY ASSOCIATED WITH THE FAT CELL PLASMA MEMBRANE

1981 ◽  
Vol 9 (2) ◽  
pp. 232P-232P
Author(s):  
G. J. Belsham ◽  
R. W. Brownsey ◽  
R. M. Denton
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Fat Cell ◽  
Cell Plasma Membrane ◽  
Cell Plasma

scholarly journals Protein Kinase Activity of Phosphoinositide 3-Kinase Regulates Cytokine-Dependent Cell Survival

PLoS Biology ◽  
2013 ◽  
Vol 11 (3) ◽  
pp. e1001515 ◽  
Author(s):  
Daniel Thomas ◽  
Jason A. Powell ◽  
Benjamin D. Green ◽  
Emma F. Barry ◽  
Yuefang Ma ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Survival ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Dependent Cell ◽  
Phosphoinositide 3 Kinase

Early phosphoinositide 3-kinase activity is required for late activation of protein kinase Cε in platelet-derived-growth-factor-stimulated cells: evidence for signalling across a large temporal gap

2001 ◽  
Vol 358 (2) ◽  
pp. 281-285 ◽  
Author(s):  
Egle BALCIUNAITE ◽  
Andrius KAZLAUSKAS
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Recent Observation ◽  
Time Interval ◽  
Long Time ◽  
Subsequent Activation ◽  
Phase Interval ◽  
Phosphoinositide 3 Kinase

At least two signalling systems have the potential to contribute to the activation of protein kinase C (PKC) family members such as PKC∊. One of these is phosphoinositide 3-kinase (PI 3-kinase), whose lipid products activate PKC∊ in vitro and in living cells. The recent observation that there are multiple waves of PI 3-kinase and PKC∊ activity within the G0-to-S phase interval provides a new opportunity to investigate the relationship between these two signalling enzymes in vivo. We have assessed the relative importance of the early and late waves of PI 3-kinase activity for the corresponding waves of PKC∊ activity. Blocking the first phase of PI 3-kinase activity inhibited both early and late activation of PKC∊. In contrast, the second wave of PI 3-kinase activity was dispensable for late activation of PKC∊. These findings suggested that early PI 3-kinase activation induced a stable change in PKC∊, which predisposed it to subsequent activation by lipid cofactors. Indeed, partial proteolysis of PKC∊ indicated that early activation of PI 3-kinase led to a conformation change in PKC∊ that persisted as the activity of PKC∊ cycled. We propose a two-step hypothesis for the activation of PKC∊ in vivo. One step is stable and depends on PI 3-kinase, whereas the other is transient and may depend on the availability of lipid cofactors. Finally, these studies reveal that PI 3-kinase and PKC∊ are capable of communicating over a relatively long time interval and begin to elucidate the mechanism.

Phosphoinositide 3-kinase: the protein kinase that time forgot

2004 ◽  
Vol 32 (2) ◽  
pp. 330-331 ◽  
Author(s):  
L.C. Foukas ◽  
P.R. Shepherd
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Class I ◽  
Protein Kinase Activity ◽  
Lipid Kinase ◽  
Vast Amount ◽  
Lipid Kinases ◽  
Phosphoinositide 3 Kinase ◽  
In Cells

Class I phosphoinositide 3-kinases were originally characterized as lipid kinases, although more than 10 years ago they were also found to phosphorylate protein serine residues. However, while there is a vast amount of data on the function of this lipid kinase activity, relatively little is known about the function of the protein kinase activity. We discuss the evidence that suggests that the protein kinase activity of phosphoinositide 3-kinases mediates important signalling functions in cells.

scholarly journals PI3Kγ controls oxidative bursts in neutrophils via interactions with PKCα and p47phox

2009 ◽  
Vol 419 (3) ◽  
pp. 603-610 ◽  
Author(s):  
Katja Lehmann ◽  
Jörg P. Müller ◽  
Bernhard Schlott ◽  
Philipp Skroblin ◽  
Dagmar Barz ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Direct Interaction ◽  
Protein Kinase Activity ◽  
Ros Production ◽  
Oxygen Species ◽  
Regulatory Module ◽  
Protein Kinase Cα ◽  
Inflammatory Immune Response ◽  
Phosphoinositide 3 Kinase

Neutrophils release reactive oxygen species (ROS) as part of the innate inflammatory immune response. Phosphoinositide 3-kinase γ (PI3Kγ), which is induced by the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP), has been identified as an essential intracellular mediator of ROS production. However, the complex signalling reactions that link PI3Kγ with ROS synthesis by NADPH oxidase have not yet been described in detail. We found that activation of neutrophils by fMLP triggers the association of PI3Kγ with protein kinase Cα (PKCα). Specific inhibition of PI3Kγ suppresses fMLP-mediated activation of PKCα activity and ROS production, suggesting that the protein kinase activity of PI3Kγ is involved. Our data suggest that the direct interaction of PI3Kγ with PKCα forms a discrete regulatory module of fMLP-dependent ROS production in neutrophils.

Protein kinase activity of phosphoinositide 3-kinase regulates β-adrenergic receptor endocytosis

2005 ◽  
Vol 7 (8) ◽  
pp. 785-796 ◽  
Author(s):  
Sathyamangla V. Naga Prasad ◽  
Arundathi Jayatilleke ◽  
Aasakiran Madamanchi ◽  
Howard A. Rockman
Keyword(s):  
Protein Kinase ◽  
Adrenergic Receptor ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Receptor Endocytosis ◽  
Phosphoinositide 3 Kinase
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