Kinases AKT/protein kinase B

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... 

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... 

Brognard, J., Clark, A.S., Ni, Y., and Dennis. P.A. 2001. Akt/protein kinase b is constitutively active in nonsmall cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. 

I. The phosphatidylinositide 3-kinase (PI 3-kinase) pathway, in particular, effects mediated through its effector protein kinase B (PKB, also termed Akt three isoforms) ... 

An application of this synthetic strategy by the same group led to the development of a series of potent and selective allosteric Akt (protein kinase B/PKB) kinase inhibitors that induced apoptosis in tumor cells and inhibited Akt phosphorylation in vivo (Scheme 6.261) [451]. 

Akama, K. T. and McEwen, B. S. Estrogen stimulates post-synaptic density-95 rapid protein synthesis via the Akt/ protein kinase B pathway. /. Neurosci. 23 2333-2339,2003. 

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]. 

Carson, J.P., KuUk, G., Weber, M.J. 1999, Antiapoptotic signaling in LNCaP prostate cancer cells a survival signaling pathway independent of phosphatidylinositol 3 -kinase and Akt/protein kinase B. Cancer Res Apr 59 1449-1453... 

Persad, S., AttweU, S. Gray, V., Delcomenne, M., Troussard, A., Sanghera, J., and Dedhar, S., 2000, Inhibition of integrin-hnked kinase (ILK) suppresses activation of protein kinase B/Akt and induces ceU cycle arrest and apoptosis of PTFN-mutant prostate cancer cells. 

Protein kinase B (PKB), which is also known as Akt, is a serine/threonine kinase that also belongs to the AGC kinase subtype. Three mammalian isoforms—PKBo , /3, and y have been identified. These proteins are broadly expressed and, although isoform-specific patterns of expression exists in some tissues, the three kinases have a similar organizational structure an amino-terminal PH domain, a central serine/threonine catalytic domain, and a short regulatory region at the carboxy terminal end containing the so-called hydrophobic motif [118-120]. 

Triciribine, also known as Akt/protein kinase B signaling inhibitor-2 (API-2) compound 52, Fig. 9), was identified by screening the National Cancer Institute Diversity Set chemical library (1992 compounds). The screen was performed using a cell-based proliferation assay with PKB/1 transformed NIH3T3 cells, and triciribine scored positive in this assay with an IC50 value of 50 nM [ 196]. Although the compound blocks the cellular phosphorylation... 

Burgering BM, Burgering BM, Coffer PJ. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 1995 376(6541) 599-602. 

Protein kinase B (Akt) is a serine/threonine, mitogen-regulated protein kinase involved in the protection of cells from apoptosis as well as the promotion of cell proliferation and diverse metabolic responses. It is activated upon binding of phospholipids and phosphorylation at residues Thr and Ser by upstream kinases such as phosphoinositide-dependent protein kinase 1 and 2 (M15). Activation of... 

The PI3 kinase (PI3-K) is translocated to the membrane by interaction of the SH2 domain of its p85 subunit with phosphotyrosine residues of the activated receptor. There it converts PtdIns(3,4)P2.into PtdIns(3,4,5)P3 which binds to PH domains of various effector molecules and recruits them into the signaling chain. The effector molecules can stimulate cell division or can induce the programmed cell death. The tumor suppressor PTEN hydrolyses phosphates from PtdIns(3,4,5)P3 and thus inhibits the growth promoting effect of the PI3 kinase signaling. An important effector of PI3 kinase is the protein kinase Akt which is also termed protein kinase B (PKB). GF growth factor GFR growth factor receptor. 

An important target protein of Ptdlns(3,4,5)P3 is Akt kinase, also known as protein kinase B (PKB). The signahng pathway for Akt kinase shown in Fig. 6.9b illustrates the role of P13-kinase and Ptdlns(3,4,5)P3 in growth factor controlled signal pathways that lead from the cell membrane into the cytosol and the nucleus. 

Li, Q., Zhu, G.D. (2002) Targeting ser-ine/threonine protein kinase B/Akt and cell-cycle checkpoint kinases for treating cancer. Curr Top Med Chem.2, 939-971. 

Tremblay, R Lavigne, C. Jacques, H. Marette, A. Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alterations in both Akt/protein kinase B and atypical protein kinase C (z/1) activities. Diabetes, 50, 1901-1910 (2001)... 

Wang, D. Sul, H.S. Insulin stimulation of the fatty acid synthase promoter is mediated by the phosphatidylinositol 3-kinase pathway. Involvement of protein kinase B/Akt. J. Biol. Chem., 273, 25420-25426 (1998)... 

The A3 Receptor and the Phosphatidylinositol 3-Kinase/ Protein Kinase B/Nuclear Factor-kB (PI3-K/AKT/NF-kB) Signal Transduction Cascade... 

Chaudhary LR, Hruska KA. 2003. Inhibition of cell survival signal protein kinase B/Akt by curcumin in human prostate cancer cells. J Cell Biochem 89 1-5. 

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