Serine-threonine protein kinase AKT

The interaction between Bc1-Xl and Bad is regulated by phosphorylation by the serine/threonine protein kinase Akt (or protein kinase B), a member of the PtdIns-3,4,5-P3-regulated pathway. This scenario is summarized in Fig. 13.9. Akt... 

Dudek H, Datta SR, Franke TF, et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997 275 661-665. 

In turn, MAPKs are also involved in the regulation of the gene expression of all three NOS isoenzymes. The expression of iNOS (NOS-2) is regulated by all three MAP kinase pathways in a variety of cell types [125-129]. For example, INK and ERKl/2 pathways are necessary for lipopolysaccharide (LPS-) and interferon-y-stimulated iNOS expression in mouse macrophage cells, possibly via a-tumor necrosis factor secretion, whereas p38 inhibited induction [130]. The induction of endothelial NOS (eNOS, NOS-3) by estrogen, fibroblast growth factor, or epidermal growth factor in endothelial cells involves the Ras-ERK pathway [131,132]. eNOS is phosphorylated, and thus activated, by the serine/threonine protein kinase Akt, which is recruited to the cell membrane by PI3-kinase as an antiapoptotic mechanism in the response of endothelial cells to shear stress [133]. 

Protein kinase B, or Akt, was discovered as the product of an oncogene of the acutely transforming retrovirus AKT8, causing T-cell lymphomas in mice. It encodes a fusion product of a cellular serine/threonine protein kinase and the viral structural protein Gag. This kinase is similar to both protein kinase Ce (PKCe 73% identity to the catalytic domain) and protein kinase A (PKA 68%). It differs from other protein kinases in that it contains a pleckstrin homology (PH) domain, which allows it to bind to polyphosphoinositide head groups (and also to G-protein fly subunits). To date, three subtypes have been identified a, (3, and y, all of which show a broad tissue distribution. It... 

Studies in breast cancer demonstrate that stem cell populations are more resistant to radiation treatment and Wnt/P-catenin signaling mediates the resistance. These CSCs populations exhibit altered DNA repair in response to radiation and increased AKT (a serine-threonine protein kinase) and P-catenin activities. Blocking the AKT and P-catenin activation by inhibitor perifosine sensitizes the cells to radiation. These studies have underscored the importance of Wnt signaling in breast cancer and the targets for effective therapeutics. 

Tinoco et al. provided structural characterization of a neuroblast-specific phosphorylated region of myristoylated alanine-rich C kinase substrate (MARCKS), a protein that interacts with actin, Ca -calmodu-lin, and plasma membrane lipids and is specifically phosphorylated by protein kinase C (PKC). By using high-resolution field-cycling P-NMR spectroscopy and a spin-labeled recombinant PH domain of Akt 1 RAC-a serine/threonine-protein kinase Gradziel et al. provided evidence that anticancer cytotoxic amphiphiles (perifosine and miltefosine) and... 

Under the influence of insulin (and other hormones or growth factors), a signaling chain is activated that results in the activation of the serine/threonine-specific protein kinase Akt/PKB (see Section6.6.3) and in the phosphorylation of 4E-BP1. It is assumed that the phosphorylation of 4E-BP1 represents the signal for the release of... 

A new signaling pathway of the H3 receptor involving receptor modulation of the activity of the serine/threonine-specific protein kinase Akt (protein kinase B, PKB)/GSK-3p (glycogen... 

Tyrosine phosphorylated IRS interacts with and activates PI 3-kinase [3]. Binding takes place via the SRC homology 2 (SH2) domain of the PI 3-kinase regulatory subunit. The resulting complex consisting of INSR, IRS, and PI 3-kinase facilitates interaction of the activated PI 3-kinase catalytic subunit with the phospholipid substrates in the plasma membrane. Generation of PI 3-phosphates in the plasma membrane reemits phospholipid dependent kinases (PDKl and PDK2) which subsequently phosphorylate and activate the serine/threonine kinase Akt (synonym protein... 

AKT-1 kinase (also called protein kinase B or PKBa) is a serine/threonine kinase belonging to the AGC kinase family [1], AKT was identified from a viral oncogene, v-akt, found in tumor lines established from spontaneous thymomas found in AKR mice [2]. Subsequently, two more AKT isoforms, AKT-2 (or PKB(3) and AKT-3 (or PKBy) have been identified [3]. Reviews exist detailing the structural and cell biology of AKT and the reader is referred to these for further information [4,7,12]. 

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