Differential Regulation of Glycogen Synthase Kinase 3β by Insulin and Wnt Signaling

Ding, Vivianne W.; Chen, Ruihong; McCormick, Frank

doi:10.1074/jbc.m005342200

Cited by 407 publications

(384 citation statements)

References 55 publications

(69 reference statements)

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“…Some cases of cross talk between Wnt and insulin pathways have been reported (Fukumoto et al, 2001;Harwood, 2001), including on ␤-catenin activity (Papkoff, 1997;Playford et al, 2000;Desbois-Mouthon et al, 2001). The pool of GSK-3 targeted by Wnt is mostly nonphosphorylated by the insulin/PKB pathway (Ding et al, 2000). However, a report by Fukumoto et al, (2001) shows a role of PKB/Akt in the multiprotein complex containing Dvl, Axin, ␤-catenin, and GSK-3.…”

Section: Gsk-3 Inhibition Is One Component In the Initiation Of Diffementioning

confidence: 95%

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Rochat

Fernandez

Vandromme

et al. 2004

MBoC

129

115

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During ex vivo myoblast differentiation, a pool of quiescent mononucleated myoblasts, reserve cells, arise alongside myotubes. Insulin/insulin-like growth factor (IGF) and PKB/Akt-dependent phosphorylation activates skeletal muscle differentiation and hypertrophy. We have investigated the role of glycogen synthase kinase 3 (GSK-3) inhibition by protein kinase B (PKB)/Akt and Wnt/␤-catenin pathways in reserve cell activation during myoblast differentiation and myotube hypertrophy. Inhibition of GSK-3 by LiCl or SB216763, restored insulin-dependent differentiation of C2ind myoblasts in low serum, and cooperated with insulin in serum-free medium to induce MyoD and myogenin expression in C2ind myoblasts, quiescent C2 or primary human reserve cells. We show that LiCl treatment induced nuclear accumulation of ␤-catenin in C2 myoblasts, thus mimicking activation of canonical Wnt signaling. Similarly to the effect of GSK-3 inhibitors with insulin, coculturing C2 reserve cells with Wnt1-expressing fibroblasts enhanced insulinstimulated induction of MyoD and myogenin in reserve cells. A similar cooperative effect of LiCl or Wnt1 with insulin was observed during late ex vivo differentiation and promoted increased size and fusion of myotubes. We show that this synergistic effect on myotube hypertrophy involved an increased fusion of reserve cells into preexisting myotubes. These data reveal insulin and Wnt/␤-catenin pathways cooperate in muscle cell differentiation through activation and recruitment of satellite cell-like reserve myoblasts. INTRODUCTIONSatellite cells are skeletal muscle adult stem cells that participate in postnatal muscle growth and regeneration. Although satellite cells are normally quiescent in adult muscle, they are responsible for muscle regeneration after injury and involved in work-or load-induced muscle fiber hypertrophy (Rosenblatt and Parry, 1992;Schultz and McCormick, 1994;De Angelis et al., 1999;Semsarian et al., 1999;Bodine et al., 2001).Ex vivo models such as myogenic cell lines were isolated from adult mouse muscle and as such are derived from adult satellite cells. At the proliferative stage, myoblasts (activated satellite cells) can be grown extensively in high serum-containing medium and express MyoD, a musclespecific transcription factor that regulates the differentiation process (Weintraub, 1993). When serum levels are lowered, myoblasts exit the cell cycle and spontaneously differentiate, giving rise to a heterogeneous population of cells. The first and major subpopulation is composed of myotubes, quiescent multinucleated cells expressing muscle-specific structural proteins. The remaining subset is composed of quiescent, mononucleated and undifferentiated cells termed reserve cells. Reserve cells retain the ability to be activated and proliferate after which they can be induced to differentiate, leading again to a new mixed population of myotubes and reserve cells. They also express at least two genes characteristic of skeletal muscle stem cells, namely, myf-5 and cd34 and from these c...

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Section: Gsk-3 Inhibition Is One Component In the Initiation Of Diffementioning

confidence: 95%

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Rochat

Fernandez

Vandromme

et al. 2004

MBoC

129

115

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“…Unlike insulin, however, Wnt signaling does not obviously affect the phosphorylation state of GSK3 (Ding et al, 2000). Intriguingly, while most of the GSK3 in the cell is inhibited by Wnt signaling, the enzymatic activity of the small amount of GSK3 bound to Axin is not inhibited, suggesting that this pool of GSK3 might be in a special protected state (Ding et al, 2000). In support of this, overexpression of an activated form of the insulin pathway kinase Akt suppressed GSK3 enzymatic activity but did not increase b-catenin levels .…”

Section: B-cateninmentioning

confidence: 97%

“…Several signaling pathways, most notably the insulin pathway, inhibit GSK3 by phosphorylating serine 9 (Ser9) on GSK3 (reviewed by Cohen and Frame (2001)). GSK3 activity measured in semi-purified preparations using a peptide substrate is inhibited by insulin signaling very rapidly, with a maximum effect occurring 10 min after stimulation (Cook et al, 1996;Ding et al, 2000). Unlike insulin, however, Wnt signaling does not obviously affect the phosphorylation state of GSK3 (Ding et al, 2000).…”

Section: B-cateninmentioning

confidence: 98%

“…GSK3 activity measured in semi-purified preparations using a peptide substrate is inhibited by insulin signaling very rapidly, with a maximum effect occurring 10 min after stimulation (Cook et al, 1996;Ding et al, 2000). Unlike insulin, however, Wnt signaling does not obviously affect the phosphorylation state of GSK3 (Ding et al, 2000). Intriguingly, while most of the GSK3 in the cell is inhibited by Wnt signaling, the enzymatic activity of the small amount of GSK3 bound to Axin is not inhibited, suggesting that this pool of GSK3 might be in a special protected state (Ding et al, 2000).…”

Section: B-cateninmentioning

confidence: 99%

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β-Catenin destruction complex: insights and questions from a structural perspective

2006

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At the heart of the canonical Wnt signaling pathway is the b-catenin destruction complex, which functions in the absence of Wnt signaling to keep the cytosolic and nuclear levels of b-catenin very low by promoting the phosphorylation and ubiquitination of b-catenin. Structural studies, combined with other experimental approaches, have begun to provide important insights into the mechanism of the destruction complex. We suggest a working model for the destruction complex based on the existing structural and experimental data, and focus on the questions that this model and other studies have raised about the function of the complex in both the normal and Wnt-inhibited states.

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“…Some important downstream targets of PI3K include the phosphorylation of Akt and glycogen synthase kinase‐3β. Increased levels of p‐glycogen synthase kinase‐3β stabilize and accumulate β‐catenin in the cytosol, which is followed by translocation into the nucleus 35. β‐Catenin is known to be a strong mediator of angiogenesis 36.…”

Section: Discussionmentioning

confidence: 99%

Disruption of VEGF Mediated Flk‐1 Signaling Leads to a Gradual Loss of Vessel Health and Cardiac Function During Myocardial Infarction: Potential Therapy With Pellino‐1

Thirunavukkarasu

Selvaraju

Joshi

et al. 2018

JAHA

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BackgroundThe present study demonstrates that the ubiquitin E3 ligase, Pellino‐1 (Peli1), is an important angiogenic molecule under the control of vascular endothelial growth factor (VEGF) receptor 2/Flk‐1. We have previously reported increased survivability of ischemic skin flap tissue by adenovirus carrying Peli1 (Ad‐Peli1) gene therapy in Flk‐1+/− mice.Methods and ResultsTwo separate experimental groups of mice were subjected to myocardial infarction (MI) followed by the immediate intramyocardial injection of adenovirus carrying LacZ (Ad‐LacZ) (1×109 pfu) or Ad‐Peli1 (1×109 pfu). Heart tissues were collected for analyses. Compared with wild‐type (WTMI) mice, analysis revealed decreased expressions of Peli1, phosphorylated (p‐)Flk‐1, p‐Akt, p‐eNOS, p‐MK2, p‐IκBα, and NF‐κB and decreased vessel densities in Flk‐1+/− mice subjected to MI (Flk‐1+/− MI). Mice (CD1) treated with Ad‐Peli1 after the induction of MI showed increased β‐catenin translocation to the nucleus, connexin 43 expression, and phosphorylation of Akt, eNOS, MK2, and IκBα, that was followed by increased vessel densities compared with the Ad‐LacZ–treated group. Echocardiography conducted 30 days after surgery showed decreased function in the Flk1+/− MI group compared with WTMI, which was restored by Ad‐Peli1 gene therapy. In addition, therapy with Ad‐Peli1 stimulated angiogenic and arteriogenic responses in both CD1 and Flk‐1+/− mice following MI. Ad‐Peli1 treatment attenuated cardiac fibrosis in Flk‐1+/− MI mice. Similar positive results were observed in CD1 mice subjected to MI after Ad‐Peli1 therapy.ConclusionOur results show for the first time that Peli1 plays a unique role in salvaging impaired collateral blood vessel formation, diminishes fibrosis, and improves myocardial function, thereby offering clinical potential for therapies in humans to mend a damaged heart following MI.

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Differential Regulation of Glycogen Synthase Kinase 3β by Insulin and Wnt Signaling

Cited by 407 publications

References 55 publications

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

Insulin and Wnt1 Pathways Cooperate to Induce Reserve Cell Activation in Differentiation and Myotube Hypertrophy

β-Catenin destruction complex: insights and questions from a structural perspective

Disruption of VEGF Mediated Flk‐1 Signaling Leads to a Gradual Loss of Vessel Health and Cardiac Function During Myocardial Infarction: Potential Therapy With Pellino‐1

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