Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα
Dario R. Alessi,Stephen R. James,C. Peter Downes,Andrew B. Holmes,Piers R. J. Gaffney,Colin B. Reese,Philip Cohen +6 more
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In this paper, a protein kinase that phosphorylates PKB α at Thr308 and increases its activity over 30-fold was found to play a key role in mediating the activation of PKB by insulin and growth factors.About:
This article is published in Current Biology.The article was published on 1997-04-01 and is currently open access. It has received 2866 citations till now. The article focuses on the topics: Mitogen-activated protein kinase kinase & Akt/PKB signaling pathway.read more
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Cell signaling by receptor-tyrosine kinases
TL;DR: Understanding of the complex signaling networks downstream from RTKs and how alterations in these networks are translated into cellular responses provides an important context for therapeutically countering the effects of pathogenic RTK mutations in cancer and other diseases.
Journal ArticleDOI
Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery
Sandeep Robert Datta,Henryk Dudek,Xu Tao,Shane C. Masters,Haian Fu,Yukiko Gotoh,Michael E. Greenberg +6 more
TL;DR: It is shown that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival.
Journal ArticleDOI
The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
Igor Vivanco,Charles L. Sawyers +1 more
TL;DR: Small-molecule therapeutics that block PI3K signalling might deal a severe blow to cancer cells by blocking many aspects of the tumour-cell phenotype.
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Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
TL;DR: In this paper, the rictor-mTOR complex was used to identify compounds which modulate Akt activity mediated by the Rictor mTOR complex and methods for treating or preventing a disorder that is associated with aberrant Akt activation.
Journal ArticleDOI
Insulin signalling and the regulation of glucose and lipid metabolism
Alan R. Saltiel,C. Ronald Kahn +1 more
TL;DR: The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide, and tissues such as muscle, fat and liver become less responsive or resistant to insulin.
References
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A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
TL;DR: This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr with little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose.
Journal ArticleDOI
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.
TL;DR: It is shown that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3, and it is demonstrated that PKB is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC).
Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15 (23):6541-6551
TL;DR: It is demonstrated that activation of PKBalpha by insulin or insulin‐like growth factor‐1 (IGF‐1) results from phosphorylation of both Thr308 and Ser473, that phosphorylate of both residues is critical to generate a high level of P KBalpha activity and that the phosphorylated of Thr308 in vivo is not dependent on phosphorylations of Ser473 or vice versa.
Journal ArticleDOI
Mechanism of activation of protein kinase B by insulin and IGF-1.
Dario R. Alessi,Mirjana Andjelkovic,Barry Caudwell,Peter Cron,Nick Morrice,Philip Cohen,Brian A. Hemmings +6 more
TL;DR: In this paper, the activation of PKBalpha was accompanied by its phosphorylation at Thr308 and Ser473 and, like activation, likeactivation was prevented by the phosphatidylinositol 3-kinase inhibitor wortmannin.
Journal ArticleDOI
Regulation of Neuronal Survival by the Serine-Threonine Protein Kinase Akt
Henryk Dudek,Sandeep Robert Datta,Thomas F. Franke,Morris J. Birnbaum,Ryoji Yao,Geoffrey M. Cooper,Rosalind A. Segal,David R. Kaplan,Michael E. Greenberg +8 more
TL;DR: Findings suggest that in the developing nervous system, Akt is a critical mediator of growth factor-induced neuronal survival.