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AKT2 INS (1 - 7 of 7)
PMID: 12808134
Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing.
... primary role of Akt2 in insulin signaling ...   (details)

AKT2 INS

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 12808134

Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing.
Source

Proceedings of the National Academy of Sciences of the United States of America (6/24/2003)

Abstract

Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Glucose homeostasis is controlled by insulin in part through the translocation of intracellular glucose transporter 4 to the plasma membrane in muscle and fat cells. Akt/protein kinase B downstream of phosphatidylinositol 3-kinase has been implicated in this insulin-signaling pathway, but results with a variety of reagents including Akt1-/- and Akt2-/- mice have been equivocal. Here we report the application of small interfering RNA-directed gene silencing to deplete both Akt1 and Akt2 in cultured 3T3-L1 adipocytes. Loss of Akt1 alone slightly impaired insulin-mediated hexose transport activity but had no detectable effect on glycogen synthase kinase (GSK) -3 phosphorylation. In contrast, depletion of Akt2 alone by 70% inhibited approximately half of the insulin responsiveness. Combined depletions of Akt1 plus Akt2 in these cells even more markedly attenuated insulin action on glucose transporter 4 movements, hexose transport activity, and GSK-3 phosphorylation. These data demonstrate a primary role of Akt2 in insulin signaling, significant functional redundancy of Akt1 and Akt2 isoforms in this pathway, and an absolute requirement of Akt protein kinases for regulation of glucose transport and GSK-3 in cultured adipocytes.

PMID: 15753124
Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles.
... that insulin activation of Akt2 specifically ...   (details)

AKT2 INS

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 15753124

Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles.
Source

The Journal of cell biology (3/14/2005)

Abstract

Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. We have identified an unusual potential dual Akt/protein kinase B consensus phosphorylation motif in the protein Synip (RxKxRS (97) xS (99)). Surprisingly, serine 97 is not appreciably phosphorylated, whereas serine 99 is only a specific substrate for Akt2 but not Akt1 or Akt3. Although wild-type Synip (WT-Synip) undergoes an insulin-stimulated dissociation from Syntaxin4, the Synip serine 99 to phenylalanine mutant (S99F-Synip) is resistant to Akt2 phosphorylation and fails to display insulin-stimulated Syntaxin4 dissociation. Furthermore, overexpression of WT-Synip in 3T3L1 adipocytes had no effect on insulin-stimulated recruitment of glucose transporter 4 (GLUT4) to the plasma membrane, whereas overexpression of S99F-Synip functioned in a dominant-interfering manner by preventing insulin-stimulated GLUT4 recruitment and plasma membrane fusion. These data demonstrate that insulin activation of Akt2 specifically regulates the docking/fusion step of GLUT4-containing vesicles at the plasma membrane through the regulation of Synip phosphorylation and Synip-Syntaxin4 interaction.

PMID: 20022950
Dissecting the mechanism of insulin resistance using a novel heterodimerization strategy to activate Akt.
... rendered insulin-resistant either ... of Akt2 stimulated hemagglutinin ...   (details)

AKT2 INS

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 20022950

Dissecting the mechanism of insulin resistance using a novel heterodimerization strategy to activate Akt.
Source

The Journal of biological chemistry (2/19/2010)

Abstract

Dissecting the mechanism of insulin resistance using a novel heterodimerization strategy to activate Akt. Insulin resistance can occur in response to many different external insults, including chronic exposure to insulin itself as well as other agonists such as dexamethasone. It is generally thought that such defects arise due to a defect (s) at an early stage in the insulin signaling cascade. One model suggests that this involves activation of the mammalian target of rapamycin/S6 kinase pathway, which inactivates insulin receptor substrate via Ser/Thr phosphorylation. However, we have recently shown that insulin receptor substrate is not a major node for insulin resistance defects. To explore the mechanism of insulin resistance, we have developed a novel system to activate Akt independently of its upstream effectors as well as other insulin-responsive pathways such as mitogen-activated protein kinase. 3T3-L1 adipocytes were rendered insulin-resistant either with chronic insulin or dexamethasone treatment, but conditional activation of Akt2 stimulated hemagglutinin-tagged glucose transporter 4 translocation to the same extent in these insulin-resistant and control cells. However, addition of insulin to cells in which Akt was conditionally activated resulted in a reversion to the insulin-resistant state, indicating a feedforward inhibitory mechanism activated by insulin itself. This effect was overcome with wortmannin, implicating a role for phosphatidylinositol 3-kinase in this inhibitory process. We conclude that in chronic insulin- and dexamethasone-treated cells, acute activation with insulin itself is required to activate a feedforward inhibitory pathway likely emanating from phosphatidylinositol 3-kinase that converges on a target downstream of Akt to cause insulin resistance.

PMID: 9512493
Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha.
Insulin induced the ... of PKBbeta.   (details)

AKT2 INS

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 9512493

Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha.
Source

The Biochemical journal (4/1/1998)

Abstract

Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha. The regulatory and catalytic properties of the three mammalian isoforms of protein kinase B (PKB) have been compared. All three isoforms (PKBalpha, PKBbeta and PKBgamma) were phosphorylated at similar rates and activated to similar extents by 3-phosphoinositide-dependent protein kinase-1 (PDK1). Phosphorylation and activation of each enzyme required the presence of PtdIns (3,4,5) P3 or PtdIns (3,4) P2, as well as PDK1. The activation of PKBbeta and PKBgamma by PDK1 was accompanied by the phosphorylation of the residues equivalent to Thr308 in PKBalpha, namely Thr309 (PKBbeta) and Thr305 (PKBgamma). PKBgamma which had been activated by PDK1 possessed a substrate specificity identical with that of PKBalpha and PKBbeta towards a range of peptides. The activation of PKBgamma and its phosphorylation at Thr305 was triggered by insulin-like growth factor-1 in 293 cells. Stimulation of rat adipocytes or rat hepatocytes with insulin induced the activation of PKBalpha and PKBbeta with similar kinetics. After stimulation of adipocytes, the activity of PKBbeta was twice that of PKBalpha, but in hepatocytes PKBalpha activity was four-fold higher than PKBbeta. Insulin induced the activation of PKBalpha in rat skeletal muscle in vivo, with little activation of PKBbeta. Insulin did not induce PKBgamma activity in adipocytes, hepatocytes or skeletal muscle, but PKBgamma was the major isoform activated by insulin in rat L6 myotubes (a skeletal-muscle cell line).

PMID: 9620559
Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin.
... the activation of AKT2 by insulin.   (details)

AKT2 INS

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 9620559

Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin.
Source

Oncogene (5/7/1998)

Abstract

Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Akt2 encodes a protein-serine/threonine kinase containing a pleckstrin homology domain characteristic of many signaling molecules. Although there has been extensive interest in the mechanism by which the closely-related Akt kinase participates in phosphatidylinositol 3-kinase-mediated signaling, comparatively little is known regarding the expression and function of Akt2. This manuscript is the first to describe Akt2 mRNA expression in the developing mouse and the activation of AKT2 by insulin. These studies demonstrate that Akt2 is especially abundant in brown fat and, to a lesser extent, skeletal muscle and liver, tissues which are highly insulin-responsive and play a role in glucose metabolism. Endogenous Akt2 expression also is upregulated in fully-differentiated C2C12 myotubes and 3T3-L1 adipocytes, suggesting that these murine cell lines represent useful in vitro models for studies of Akt2 function. We show that HA-tagged AKT2 is activated in response to insulin stimulation in vitro and that activation of AKT2 is not induced in cells pretreated with wortmannin, an inhibitor of phosphatidylinositol 3-kinase. These data suggest that Akt2 expression is fundamental to the differentiated state of fat and muscle cells and that activation of AKT2 kinase by insulin is mediated through the phosphatidylinositol 3-kinase signaling pathway.

... that Akt2 expression ... by insulin is mediated through ...   (details)

AKT2 INS

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 9620559

Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin.
Source

Oncogene (5/7/1998)

Abstract

Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Akt2 encodes a protein-serine/threonine kinase containing a pleckstrin homology domain characteristic of many signaling molecules. Although there has been extensive interest in the mechanism by which the closely-related Akt kinase participates in phosphatidylinositol 3-kinase-mediated signaling, comparatively little is known regarding the expression and function of Akt2. This manuscript is the first to describe Akt2 mRNA expression in the developing mouse and the activation of AKT2 by insulin. These studies demonstrate that Akt2 is especially abundant in brown fat and, to a lesser extent, skeletal muscle and liver, tissues which are highly insulin-responsive and play a role in glucose metabolism. Endogenous Akt2 expression also is upregulated in fully-differentiated C2C12 myotubes and 3T3-L1 adipocytes, suggesting that these murine cell lines represent useful in vitro models for studies of Akt2 function. We show that HA-tagged AKT2 is activated in response to insulin stimulation in vitro and that activation of AKT2 is not induced in cells pretreated with wortmannin, an inhibitor of phosphatidylinositol 3-kinase. These data suggest that Akt2 expression is fundamental to the differentiated state of fat and muscle cells and that activation of AKT2 kinase by insulin is mediated through the phosphatidylinositol 3-kinase signaling pathway.

PMID: 9712142
Translocation and activation of AKT2 in response to stimulation by insulin.
... that activation of AKT2 by insulin is ...   (details)

AKT2 INS

Type:  positive regulation
Is this interaction correct?
Yes
No

Comments

PMID: 9712142

Translocation and activation of AKT2 in response to stimulation by insulin.
Source

Journal of cellular biochemistry (9/15/1998)

Abstract

Translocation and activation of AKT2 in response to stimulation by insulin. The AKT2 oncogene encodes a protein-serine/threonine kinase that was recently shown to be activated by a variety of growth factors. In addition, we previously showed that AKT2 is abundant in brown fat and skeletal muscle, tissues that are highly insulin responsive and that play a role in glucose metabolism. In this study, we demonstrate that AKT2 is activated in response to stimulation by insulin in a dose- and time-dependent manner in human ovarian carcinoma cells and that activation of AKT2 is abolished in cells pretreated with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase). Activation of AKT2 is manifested by changes in its phosphorylation state. Immunofluorescence experiments demonstrate that AKT2 is translocated to the plasma membrane after insulin stimulation, and this translocation is abolished by wortmannin. Both wild-type AKT2 activated by insulin and constitutively active AKT2, which has been targeted to the membrane by the addition of a myristoylation signal, were found to inactivate glycogen synthase kinase-3 (GSK-3) in vitro. GSK-3 was not inactivated by a catalytically inactive AKT2 mutant. Collectively, these data indicate that activation of AKT2 by insulin is mediated by PI 3-kinase and that GSK-3 is a downstream target of AKT2, suggesting a potentially important role of AKT2 in glycogen synthesis and other GSK-3 signaling pathways.