Nike Hyperize70lmAktpkbrac-protein Kinases

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inition
Protein kinase B (PKB), also understood as Akt (PKB/Akt), is a serine/threonine phosphoryl transferase and a downstream effector of the phosphoinositol3 kinase (PI3K) signaling.
Discovery
The AKT protein kinase (also referred to as protein kinase B alternatively Rac-protein kinase) was initially identified as an sensitive altering component of the AKT8 virus insulated from a murine T cell lymphoma1, 2.
Classification
PKB/Akt belongs to the AGC subfamily of the protein kinase superfamily, which consists of 518 members in humans and is conserved from primitive metazoans to humans3.
Structural characteristics
The PKB subfamily comprises 3 mammalian isoforms, PKB , PKB and PKB (Akt1, Akt2 and Akt3 [link widoczny dla zalogowanych], respectively), which are productions of another genes and share a conserved building that includes 3 functional domains: an N-terminal pleckstrin homology (PH) domain, a chief kinase domain, and a C-terminal regulatory domain containing the hydrophobic motif (HM) phosphorylation site [FxxF(S/T)Y]4.
Mechanism of action
As PKB is a downstream component of (PI3K) signaling, namely is refreshed above (1) autophosphorylation of receptor tyrosine kinases elicited at ligands (such as insulin or additional growth factors), (2) provocation of G-protein-coupled receptors, or (3) activation of integrin signaling5, 6.
Functions
PKB/Akt plays an momentous character in all the cellular processes such for cell migration, survival [link widoczny dla zalogowanych], differentiation, as well as apoptosis7. Moreover, upregulation of Akt play namely recognized in variety of neoplasms, as well as chemoresistance8. To comprehend the role of PKB, tremendous efforts have been made to identify its physiological substrates. Most of the PKB substrates include the minimal unity series RxRxx(S/T), where x is any amino acid and S/T is the phosphorylation site. A genomewide screen using this series idea will list more than 1,000 putative Akt phosphorylation targets in persons. Degenerate peptide library approximate has also been used for screening manifold substrates for PKB/Akt9.
Reference:
1. Staal SP (1987). Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: exaggeration of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci, 84(14):5034-5037.
2. Staal SP, Hartley JW (1988). Thymic lymphoma induction by the AKT8 murine retrovirus. J Exp Med, 167(3):1259-64.
3. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC (2002). Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell, 10(1):151-62.
4. Hanada M, Feng J, Hemmings BA (2004). Structure, regulation and function of PKB/AKT--a major medical target. Biochim Biophys Acta, 1697(1-2):3-16.
5. Foster, F. M., Traer, C. J., Abraham, S. M. and Fry, M. J. (2003). The phosphoinositide (PI) 3-kinase household. J. Cell Sci., 116, 3037-3040.
6. Wymann, M. P., Zvelebil, M. and Laffargue, M.(2003). Phosphoinositide 3-kinase signallingwhich path apt target? Trends Pharmacol. Sci., 24, 366-376.
7. Song G, Ouyang G, Bao S (2005). The activation of Akt/PKB signaling track and cell survival. J Cell Mol Med [link widoczny dla zalogowanych], 9(1):59-71
8. Kim D, Dan HC, Park S, Yang L, Liu Q, Kaneko S, Ning J, He L, Yang H, Sun M, Nicosia SV, Cheng JQ (2005). AKT/PKB signaling mechanisms in cancer and chemoresistance. Front Biosci., 10:975-87.
9. Obata T, Yaffe MB, Leparc GG, Piro ET, Maegawa H, Kashiwagi A, Kikkawa R, Cantley LC (2000). Peptide and protein library screening defines optimal substrate motifs for AKT/PKB. J Biol Chem,