Disease relevance of AKT1

• Because atherosclerosis and neointimal hyperplasia colocalize in areas of disturbed shear stress, the effects of orbital shear stress (SS) on endothelial cell proliferation, protein kinase B (Akt) activation, and functional activity were analyzed using a senescence model [1].

High impact information on AKT1

• Akt/protein kinase B critically regulates the balance between cell survival and apoptosis [2].
• Endothelial nitric oxide synthase (eNOS) is activated by phosphorylation of serine 1177 by the protein kinase Akt/PKB [3].
• In endothelial cells lacking VE-cadherin, shear stress did not augment nuclear translocation of the VEGF receptor 2 and phosphorylation of Akt1 and P38 as well as transcriptional induction of a reporter gene regulated by a shear stress-responsive promoter [4].
• Flow shear stress stimulates Gab1 tyrosine phosphorylation to mediate protein kinase B and endothelial nitric-oxide synthase activation in endothelial cells [5].
• The effect of CsA was not related to inhibition of two known eNOS kinases, protein kinase B (Akt) and protein kinase A, because CsA did not affect Akt or protein kinase A activation [6].

Biological context of AKT1

• In this study, we found that either FSS or insulin stimulated insulin receptor substrate-1 (IRS-1) tyrosine and serine phosphorylation and increased IRS-1-associated phosphatidylinositol 3-kinase activity, phosphorylation of PKB Ser-473, phosphorylation of eNOS Ser-1179, and NO production [7].
• These results suggest that up-regulation of eNOS in response to cyclic stretch was mediated by two distinct pathways, [Ca(2+)](i) increases via the SA channel in an early phase (partially Akt/PKB), and PI3K-Akt/PKB pathways in a late phase [8].
• In a number of other systems, a link has been established between the PI3-K-Akt/PKB pathway and NF-kappaB activation, resulting in protection against apoptosis [9].
• We show that the two pathways are downregulated with different kinetics when the parasite is eliminated from the host cell cytoplasm and that NF-kappaB-dependent protection against apoptosis is not dependent on a functional PI3-K-Akt/PKB pathway [9].
• Activation of Akt (protein kinase B) stimulates metaphase I to metaphase II transition in bovine oocytes [10].

Anatomical context of AKT1

• Recently, we have shown that shear stress stimulates NO(*) production by the protein kinase B/Akt (Akt)-dependent mechanisms in bovine aortic endothelial cells (BAEC) (Go, Y. M., Boo, Y. C., Park, H., Maland, M. C., Patel, R., Pritchard, K. A., Jr., Fujio, Y., Walsh, K., Darley-Usmar, V., and Jo, H. (2001) J. Appl. Physiol. 91, 1574-1581) [11].
• Platelet-derived growth factor-BB and thrombin activate phosphoinositide 3-kinase and protein kinase B: role in mediating airway smooth muscle proliferation [12].
• We also demonstrate that Akt/PKB contributes, at least in part, to the proliferation of Theileria-transformed T cells [9].
• Pericytes seeded on either type of modified FN showed phosphorylation of p38 MAPK and dephosphorylation of Akt/PKB [13].
• Accumulation of Akt/PKB (protein kinase B), JNK1/2 (jun N-terminal kinases) and Aurora-A in oocytes during maturation was not affected by ROS [14].

Associations of AKT1 with chemical compounds

• CONCLUSIONS:: E2 increases NO production through an Akt/PKB dependent pathway [15].
• Correspondingly, the activities of endothelial nitric oxide synthase (eNOS) and Akt/PKB (measured by phosphorylation at serine 1,177 and serine 473, respectively), showed two peaks over time [8].
• The recombinant BH1 isoform was phosphorylated by p70 ribosomal S6 kinase (p70(s6k)), mitogen-activated protein kinase-activated protein kinase-1, and protein kinase B (PKB), whereas the recombinant BH3 isoform was a poor substrate for these protein kinases [16].
• Protein kinase B, a novel signaling protein kinase, was identified in BTSM cells and was activated by PDGF-BB and thrombin in a PtdIns 3-kinase-dependent manner; this may underlie mitogen-stimulated activation of p70(s6k) [12].
• Serotonin-induced growth of pulmonary artery smooth muscle requires activation of phosphatidylinositol 3-kinase/serine-threonine protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase 1 [17].

Enzymatic interactions of AKT1

• Finally, PKB phosphorylated eNOS in vitro at the same site phosphorylated in the cell and increased eNOS enzymatic activity by 15-20-fold [18].

Other interactions of AKT1

• Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades [16].
• Here we show that Ang-1 acting via the Tie 2 receptor induces phosphorylation of the survival serine-threonine kinase, Akt (or protein kinase B) [19].
• Further experiments showed that the protective effect of IGF-I against apoptosis is mediated by the stimulation of phosphatidylinositol 3-kinase and its downstream target, protein kinase B/Akt [20].

Analytical, diagnostic and therapeutic context of AKT1

• Phosphorylation of p38 mitogen-activated protein kinase (MAPK) and Akt/PKB were evaluated by Western blot analysis [13].
• Effects similar to those on AKT/PKB were also observed on signal transducer and activator of transcription 5b (STAT5b) [21].

References