Effects of Stimulation of AMP-activated Protein Kinase on Insulin-like Growth Factor 1- and Epidermal Growth Factor-dependent Extracellular Signal-regulated Kinase Pathway

Kim, Joungmok; Yoon, Moon‐Young; Choi, Sang-Lim; Kang, Insug; Kim, Sung‐Soo; Kim, Young-Seol; Choi, Young In; Ha, Joohun

doi:10.1074/jbc.m011579200

Cited by 78 publications

(64 citation statements)

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“…*, p Ͻ 0.05 versus vehicle. factor (27)(28)(29), which cause NO release. We next determined whether endogenous NO increased AMPK activation in HUVECs.…”

Section: No-induced Ampk Activation Is Camkk␤-dependent-mentioning

confidence: 99%

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Zhang

Xie

Dong

et al. 2008

Journal of Biological Chemistry

105

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2؉ chelator, indicating that NO-induced AMPK activation is guanylyl cyclase-mediated and calcium-dependent. Exposure of HUVECs or isolated mice aortas to either calcium ionophore A23187 or bradykinin significantly increased AMPK Thr-172 phosphorylation, which was abolished by N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Finally, A23187-or bradykinin-enhanced AMPK activation was significantly greater in aortas from wild type mice than those in the aortas of endothelial nitric oxide synthase knock-out mice. Taken together, we conclude that NO might act as an endogenous AMPK activator.The AMP-activated protein kinase (AMPK) 2 is a key enzyme in an important energy-sensing/signaling system by which cells sense and decode changes in energy status. The overall effect of AMPK activation is to switch off ATP-consuming pathways such as lipogenesis or gluconeogenesis, whereas switching on ATP-producing pathways such as fatty acid and glucose oxidation. AMPK is a protein consisting of three subunits designated ␣, ␤, and ␥. The ␣ subunit is the catalytic subunit containing the kinase domain, which transfers a phosphate from ATP to the target protein. The ␤ and ␥ subunits are considered regulatory components (1-3). All three subunits are required for expression of full activity (4).Phosphorylation of Thr-172 on the ␣ subunit by upstream kinases, AMPK kinases, results in AMPK activation. Several upstream kinases have been identified, including a complex of the tumor suppressor protein LKB1 and two accessory subunits, termed STRAD and MO25 (5, 6), and Ca 2ϩ /calmodulindependent protein kinase kinase (CaMKK), especially the CaMKK ␤ isoform (7-9). AMP also allosterically promotes phosphorylation at Thr-172 by LKB1 (10, 11). Any situation that causes an increase in cytoplasmic Ca 2ϩ will create a subsequent demand for ATP because Ca 2ϩ is immediately pumped out of the cytoplasm using ATP-driven pumps in the plasma membrane and endoplasmic reticulum. Activation of AMPK under these circumstances may represent a mechanism to anticipate the demand for ATP created by Ca 2ϩ entry. Nitric oxide (NO) is a small, highly reactive, diffusible free radical that has been implicated in many physiological and pathophysiological processes. NO exerts its effects through many ways including activation of the cGMP/protein kinase G pathway and through S-nitrosylation of proteins (12). There is an emerging body of evidence indicating a relationship between NO and AMPK expression/activity in cells (13). Such a relationship cooperatively promotes glucose and fatty acid oxidation. There is ample evidence showing that AMPK regulates NO production in cells. For example, endothelial nitric oxide synthase (eNOS) is phosphorylated by AMPK at position Ser-*

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“…*, p Ͻ 0.05 versus vehicle. factor (27)(28)(29), which cause NO release. We next determined whether endogenous NO increased AMPK activation in HUVECs.…”

Section: No-induced Ampk Activation Is Camkk␤-dependent-mentioning

confidence: 99%

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Zhang

Xie

Dong

et al. 2008

Journal of Biological Chemistry

105

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“…Consistent with our results, the inhibitory crosstalk between ERK1/2 and AMPK has been published recently. 25,26 AMPK activation by adiponectin suppressed angiotensin II-induced cardiac fibrosis through inhibition of ERK1/2 and activation of peroxisome proliferatoractivated receptor-a (PPAR-a). 25 In NIH-3T3 cells, AICAR-stimulated AMPK activation downregulated IGF-1-or epidermal growth factordependent ERK1/2 pathway and cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells

et al. 2009

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Adiponectin, an adipocyte-derived hormone, has been proposed to show antiatherogenic properties through the inhibitory effects against various growth factors. Insulin-like growth factor-1 (IGF-1) is one of the potent mitogens, which has been considered to play important roles in both atherogenesis and plaque stabilization in accordance to the phase of atherosclerosis. The aim of this study is to elucidate the adiponectin effects on IGF-1-induced cell migration and its intracellular signaling pathways in vascular smooth muscle cells (VSMCs). In this study, we assessed cell migration and several kinase activities in cultured rat aortic smooth muscle cells (RASMCs). Adiponectin pretreatment suppressed IGF-1-induced cell migration and extracellular signal-regulated kinase (ERK)1/2 activation, which is one of the major mediators for IGF-1-induced cell migration. In RASMCs, adiponectin and 5-aminoimidazole-4-carboxamide riboside (AICAR), a 5¢-AMP-activated protein kinase (AMPK) activator, stimulated AMPK activation. AMPK activation by AICAR inhibited IGF-1-induced ERK1/2 activation and cell migration in RASMCs. On the other hand, phosphorylation of Akt and Bad, proapoptotic molecules of the Bcl-2 family, which were increased by IGF-1 stimulation, was not diminished by the pretreatment with adiponectin. It was shown that adiponectin inhibited IGF-1-induced VSMC migration through suppression of ERK1/2 activation, which might be implicated in AMPK activation. Furthermore, adiponectin selectively inhibited ERK1/2 pathway, not Akt-Bad pathway, stimulated by IGF-1. From these findings, it was implied that adiponectin suppressed IGF-1-induced VSMC migration and its signaling selectivity.

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“…Previous studies have been shown that S259A-Raf is about 2.5-fold more active than the wild-type molecule (30), an effect that is sufficient to increase the expression of SM-MHC in VSM cells (18). Similarly, activation of endogenous Raf by stimulating receptor tyrosine kinases with IGF, epidermal growth factor, or NGF revealed an about 2-3-fold activation of the Raf kinase activity (44,45). In PDGFstimulated VSM cells, PI 3-kinase inhibition increased the late-phase Raf activity by about 2-fold, an effect that was sufficient to generate a prolonged ERK1/2 phosphorylation.…”

Section: Fig 6 Pi 3-kinase Inhibition Augments the Pdgf-induced Latmentioning

confidence: 99%

Regulation of Raf by Akt Controls Growth and Differentiation in Vascular Smooth Muscle Cells

Reusch

Zimmermann²,

Schaefer³

et al. 2001

Journal of Biological Chemistry

144

107

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The stimulation of platelet-derived growth factor (PDGF) receptors shifts vascular smooth muscle (VSM) cells toward a more proliferative phenotype. Thrombin activates the same signaling cascades in VSM cells, namely the Ras/Raf/MEK/ERK and the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathways. Nonetheless, thrombin was not mitogenic, but rather increased the expression of the smooth muscle-specific myosin heavy chain (SM-MHC) indicative of an in vitro re-differentiation of VSM cells. A more detailed analysis of the temporal pattern and relative signal intensities revealed marked differences. The strong and biphasic phosphorylation of ERK1/2 in response to thrombin correlated with its ability to increase the activity of the SM-MHC promoter whereas Akt was only partially and transiently phosphorylated. During progression of vascular diseases or vascular injury following balloon dilatation, the release of growth factors such as PDGF, 1 epidermal growth factor, or IGF has been shown to increase the smooth muscle cell proliferation and migration (1-3). This de-differentiation is characterized by a decreased expression of contractile proteins.Following ligand binding, tyrosine kinase receptors undergo dimerization which allows transphosphorylation at multiple tyrosine residues. The intracellular signal transduction involves direct interaction of effector molecules via specific domains, e.g. Src homology 2 domains and phosphotyrosine-binding domains. More than 10 different Src homology 2 domaincontaining molecules have been shown to bind to different autophosphorylation sites in the PDGF receptors, including signal transduction molecules with enzymatic activity like phosphatidylinositol 3-kinases (PI 3-kinases), phospholipases C␥, or Src as well as adaptor molecules such as Grb2 and Shc (4). Binding of Grb2/Sos or Shc in turn activates the small GTP-binding protein Ras which couples to the Raf/MEK/ERK cascade. The cellular response of receptor tyrosine kinase signaling is influenced by the strength and the duration of ERK1/2 phosphorylation. Depending on the cellular context, either proliferation or differentiation may result (5). Other signaling cascades initiated by PDGF receptors and their potential cross-talk is currently under extensive investigation. Phosphorylated tyrosine residues (Tyr 740 and Tyr 751 ) on the PDGF ␤-receptor recruit the PI 3-kinases ␣ and ␤ to the plasma membrane via docking of the common p85 regulatory subunit (6, 7). Upon activation, the lipid kinase activity of PI 3-kinases catalyzes the formation of PI(3,4,5)-P 3 , a well defined plasma membrane anchor for the pleckstrin homology domains of 3-phosphoinositide-dependent kinase I and protein kinase B/Akt (8). The plasma membrane recruitment exposes Akt to subsequent activation by 3-phosphoinositide-dependent kinase I and related kinases that phosphorylate Akt at Thr 308 and Ser 473 (9). Akt is a major participant in growth factor-mediated transcription and promotes cell survival by inhibiting apoptosis. These processes appear to invol...

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Effects of Stimulation of AMP-activated Protein Kinase on Insulin-like Growth Factor 1- and Epidermal Growth Factor-dependent Extracellular Signal-regulated Kinase Pathway

Abstract: AMP-activated protein kinase (AMPK) is tightly regu-Mammalian AMP-activated protein kinase (AMPK) 1 plays a key role in the regulation of energy homeostasis and is highly conserved among animals, plants, and fungi (reviewed in Refs.

Cited by 78 publications

References 50 publications

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells

Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells

Regulation of Raf by Akt Controls Growth and Differentiation in Vascular Smooth Muscle Cells

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