scholarly journals Rapid Activation by 3,5,3′-l-Triiodothyronine of Adenosine 5′-Monophosphate-Activated Protein Kinase/Acetyl-Coenzyme A Carboxylase and Akt/Protein Kinase B Signaling Pathways: Relation to Changes in Fuel Metabolism and Myosin Heavy-Chain Protein Content in Rat Gastrocnemius Muscle in Vivo

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6462-6470 ◽  
Author(s):  
Pieter de Lange ◽  
Rosalba Senese ◽  
Federica Cioffi ◽  
Maria Moreno ◽  
Assunta Lombardi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Heavy Chain ◽  
Gastrocnemius Muscle ◽  
Protein Kinase B ◽  
Acetyl Coenzyme A ◽  
Fuel Metabolism ◽  
Myosin Heavy Chain Protein ◽  
Rapid Activation ◽  
Acetyl Coenzyme A Carboxylase

Fucoidans from Cucumaria frondosa ameliorates renal interstitial fibrosis via inhibition of PI3K/Akt/NF-κB signaling pathway

2022 ◽  
Author(s):  
Zhuo-yue Song ◽  
Mengru Zhu ◽  
Jun Wu ◽  
Tian Yu ◽  
Yao Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Protein Kinase B ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Renal Interstitial Fibrosis ◽  
Cucumaria Frondosa

The effects of Cucumaria frondosa polysaccharides (CFP) on renal interstitial fibrosis via regulating phosphatidylinositol-3-hydroxykinase/protein kinase-B/Nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated in vivo and in vitro in this research. A...

scholarly journals Domain Swapping Used To Investigate the Mechanism of Protein Kinase B Regulation by 3-Phosphoinositide-Dependent Protein Kinase 1 and Ser473 Kinase

1999 ◽  
Vol 19 (7) ◽  
pp. 5061-5072 ◽  
Author(s):  
Mirjana Andjelković ◽  
Sauveur-Michel Maira ◽  
Peter Cron ◽  
Peter J. Parker ◽  
Brian A. Hemmings
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase B ◽  
Second Messengers ◽  
Activation Mechanism ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Phosphoinositide 3 Kinase ◽  
Regulatory Sites

ABSTRACT Protein kinase B (PKB or Akt), a downstream effector of phosphoinositide 3-kinase (PI 3-kinase), has been implicated in insulin signaling and cell survival. PKB is regulated by phosphorylation on Thr308 by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and on Ser473 by an unidentified kinase. We have used chimeric molecules of PKB to define different steps in the activation mechanism. A chimera which allows inducible membrane translocation by lipid second messengers that activate in vivo protein kinase C and not PKB was created. Following membrane attachment, the PKB fusion protein was rapidly activated and phosphorylated at the two key regulatory sites, Ser473 and Thr308, in the absence of further cell stimulation. This finding indicated that both PDK1 and the Ser473 kinase may be localized at the membrane of unstimulated cells, which was confirmed for PDK1 by immunofluorescence studies. Significantly, PI 3-kinase inhibitors prevent the phosphorylation of both regulatory sites of the membrane-targeted PKB chimera. Furthermore, we show that PKB activated at the membrane was rapidly dephosphorylated following inhibition of PI 3-kinase, with Ser473 being a better substrate for protein phosphatase. Overall, the results demonstrate that PKB is stringently regulated by signaling pathways that control both phosphorylation/activation and dephosphorylation/inactivation of this pivotal protein kinase.

scholarly journals NF-κB Couples Protein Kinase B/Akt Signaling to Distinct Survival Pathways and the Regulation of Lymphocyte Homeostasis In Vivo

2005 ◽  
Vol 175 (6) ◽  
pp. 3790-3799 ◽  
Author(s):  
Russell G. Jones ◽  
Sam D. Saibil ◽  
Joyce M. Pun ◽  
Alisha R. Elford ◽  
Madeleine Bonnard ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase B ◽  
Akt Signaling ◽  
Survival Pathways ◽  
Lymphocyte Homeostasis

scholarly journals Protein Kinase B Regulates T Lymphocyte Survival, Nuclear Factor κb Activation, and Bcl-XL Levels in Vivo

2000 ◽  
Vol 191 (10) ◽  
pp. 1721-1734 ◽  
Author(s):  
Russell G. Jones ◽  
Michael Parsons ◽  
Madeleine Bonnard ◽  
Vera S.F. Chan ◽  
Wen-Chen Yeh ◽  
...  
Keyword(s):  
T Cells ◽  
Protein Kinase ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Protein Kinase B ◽  
Active Form ◽  
Nuclear Factor ◽  
Clonal Deletion ◽  
Lymphocyte Survival

The serine/threonine kinase protein kinase B (PKB)/Akt mediates cell survival in a variety of systems. We have generated transgenic mice expressing a constitutively active form of PKB (gag-PKB) to examine the effects of PKB activity on T lymphocyte survival. Thymocytes and mature T cells overexpressing gag-PKB displayed increased active PKB, enhanced viability in culture, and resistance to a variety of apoptotic stimuli. PKB activity prolonged the survival of CD4+CD8+ double positive (DP) thymocytes in fetal thymic organ culture, but was unable to prevent antigen-induced clonal deletion of thymocytes expressing the major histocompatibility complex class I–restricted P14 T cell receptor (TCR). In mature T lymphocytes, PKB can be activated in response to TCR stimulation, and peptide-antigen–specific proliferation is enhanced in T cells expressing the gag-PKB transgene. Both thymocytes and T cells overexpressing gag-PKB displayed elevated levels of the antiapoptotic molecule Bcl-XL. In addition, the activation of peripheral T cells led to enhanced nuclear factor (NF)-κB activation via accelerated degradation of the NF-κB inhibitory protein IκBα. Our data highlight a physiological role for PKB in promoting survival of DP thymocytes and mature T cells, and provide evidence for the direct association of three major survival molecules (PKB, Bcl-XL, and NF-κB) in vivo in T lymphocytes.

Rab10 in insulin-stimulated GLUT4 translocation

2008 ◽  
Vol 411 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Hiroyuki Sano ◽  
William G. Roach ◽  
Grantley R. Peck ◽  
Mitsunori Fukuda ◽  
Gustav E. Lienhard
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Subcellular Distribution ◽  
Protein Kinase B ◽  
Muscle Cells ◽  
Low Density ◽  
Glut4 Translocation ◽  
Gtpase Activating Protein ◽  
Intracellular Vesicles

In fat and muscle cells, insulin stimulates the movement to and fusion of intracellular vesicles containing GLUT4 with the plasma membrane, a process referred to as GLUT4 translocation. Previous studies have indicated that Akt [also known as PKB (protein kinase B)] phosphorylation of AS160, a GAP (GTPase-activating protein) for Rabs, is required for GLUT4 translocation. The results suggest that this phosphorylation suppresses the GAP activity and leads to the elevation of the GTP form of one or more Rabs required for GLUT4 translocation. Based on their presence in GLUT4 vesicles and activity as AS160 GAP substrates, Rabs 8A, 8B, 10 and 14 are candidate Rabs. Here, we provide further evidence that Rab10 participates in GLUT4 translocation in 3T3-L1 adipocytes. Among Rabs 8A, 8B, 10 and 14, only the knockdown of Rab10 inhibited GLUT4 translocation. In addition, we describe the subcellular distribution of Rab10 and estimate the fraction of Rab10 in the active GTP form in vivo. Approx. 5% of the total Rab10 was present in GLUT4 vesicles isolated from the low-density microsomes. In both the basal and the insulin state, 90% of the total Rab10 was in the inactive GDP state. Thus, if insulin increases the GTP form of Rab10, the increase is limited to a small portion of the total Rab10. Finally, we report that the Rab10 mutant considered to be constitutively active (Rab10 Q68L) is a substrate for the AS160 GAP domain and, hence, cannot be used to deduce rigorously the function of Rab10 in its GTP form.

scholarly journals Both Saturated and n-6 Polyunsaturated Fat Diets Reduce Phosphorylation of Insulin Receptor Substrate-1 and Protein Kinase B in Muscle during the Initial Stages of in Vivo Insulin Stimulation

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5596-5603 ◽  
Author(s):  
Georgia Frangioudakis ◽  
Ji-Ming Ye ◽  
Gregory J. Cooney
Keyword(s):  
Protein Kinase ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Protein Kinase B ◽  
Insulin Receptor Substrate ◽  
Polyunsaturated Fat ◽  
Insulin Stimulation ◽  
High Fat ◽  
Fat Diets

Our aim was to determine the importance of changes in phosphorylation of key insulin signaling intermediates in the insulin resistance observed in skeletal muscle of rats fed diets high in saturated or n-6 polyunsaturated fat. We used phospho-specific antibodies to measure the time course of phosphorylation of key components of the insulin signaling pathway by immunoblotting during the initial stages of a physiological elevation in the circulating insulin concentration. The phosphorylation of insulin receptor at Tyr1162/1163 (IR Tyr1162/1163) increased over 20 min of insulin infusion, whereas the downstream phosphorylation of insulin receptor substrate-1 Tyr612 (IRS-1 Tyr612) peaked at 5 min and declined thereafter. Interestingly, phosphorylation of IRS-1 at Tyr895 continued to increase over the 20-min period, and protein kinase B (PKB) phosphorylation at Ser473 reached a plateau by 5 min, demonstrating that different profiles of phosphorylation are involved in transmission of the insulin signal despite a constant level of insulin stimulation. In muscle from rats fed high n-6 polyunsaturated or saturated fat diets, however, there was no insulin-stimulated increase in IRS-1 Tyr612 phosphorylation and a temporal difference in PKB Ser473 phosphorylation despite no difference in IR Tyr1162/1163 phosphorylation, IRS-1 Tyr895 phosphorylation, and ERK phosphorylation. These results demonstrate that under conditions of increased insulin, similar to those used to assess insulin action in vivo, chronic high-fat feeding impairs insulin signal transduction related to glucose metabolism at the level of IRS-1 Tyr612 and PKB Ser473 and that these effects are independent of the type of fat used in the high-fat diet.

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