scholarly journals Regulation of β1 Integrin Traffic and ARF6 Gtpase by Amp-Activated Protein Kinase

2021 ◽  
Author(s):  
Rehman Ata
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Cancer Progression ◽  
Membrane Traffic ◽  
Β1 Integrin ◽  
Ampk Activation ◽  
Reciprocal Regulation ◽  
Surface Receptors ◽  
Energy Stress ◽  
Amp Activated Protein Kinase

Integrins are cell surface receptors that physically bridge the extracellular matrix to the cytoskeleton and responsible for adhesion, migration, and signaling. Integrin function is intimately controlled by their membrane traffic. For example, integrins are dynamically internalized from the cell posterior and recycled to the cell anterior during cell migration. Misregulation of integrins is intimately linked with cancer progression, including metastasis and cell proliferation and survival. We have recently uncovered that integrin membrane traffic is controlled by AMP-activated protein kinase (AMPK), an energy stress sensing kinase within cells at becomes activated upon energy stress such as by an increase in cell AMP:ATP ratio. I confirmed that AMPK activation resulted in a reduction of cell surface β1-integrin. Using assays that selectively measure integrin exocytosis and endocytosis, I found that AMPK activation regulates β1-integrin recycling and possibly endocytosis. I demonstrated that AMPK regulates Arf6 localization, a key protein which regulates β1-integrin membrane traffic. I confirmed that Arf6 and clathrin are involved in reciprocal regulation, thus highlighting the possible pathway for β1-integrin regulation by AMPK.

scholarly journals Regulation of β1 Integrin Traffic and ARF6 Gtpase by Amp-Activated Protein Kinase

2021 ◽  
Author(s):  
Rehman Ata
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Cancer Progression ◽  
Membrane Traffic ◽  
Β1 Integrin ◽  
Ampk Activation ◽  
Reciprocal Regulation ◽  
Surface Receptors ◽  
Energy Stress ◽  
Amp Activated Protein Kinase

Integrins are cell surface receptors that physically bridge the extracellular matrix to the cytoskeleton and responsible for adhesion, migration, and signaling. Integrin function is intimately controlled by their membrane traffic. For example, integrins are dynamically internalized from the cell posterior and recycled to the cell anterior during cell migration. Misregulation of integrins is intimately linked with cancer progression, including metastasis and cell proliferation and survival. We have recently uncovered that integrin membrane traffic is controlled by AMP-activated protein kinase (AMPK), an energy stress sensing kinase within cells at becomes activated upon energy stress such as by an increase in cell AMP:ATP ratio. I confirmed that AMPK activation resulted in a reduction of cell surface β1-integrin. Using assays that selectively measure integrin exocytosis and endocytosis, I found that AMPK activation regulates β1-integrin recycling and possibly endocytosis. I demonstrated that AMPK regulates Arf6 localization, a key protein which regulates β1-integrin membrane traffic. I confirmed that Arf6 and clathrin are involved in reciprocal regulation, thus highlighting the possible pathway for β1-integrin regulation by AMPK.

scholarly journals The regulation of the cell surface proteome by amp-activated protein kinase

2021 ◽  
Author(s):  
Eden Ross
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Metabolic Regulation ◽  
Cultured Cells ◽  
Cellular Adhesion ◽  
Ampk Activation ◽  
And Migration ◽  
Surface Proteome ◽  
Amp Activated Protein Kinase ◽  
Cell Surface Proteome

The cell-surface proteome controls numerous cellular functions and is dynamically controlled by endocytosis and recycling under different cellular conditions. Energy stress is a state in which a cell must engage adaptive responses to ensure survival, including remodelling of the cell-surface proteome. AMP-activated protein kinase (AMPK) is an important metabolic regulator in the cell. Recent studies suggest AMPK activation may alter the endocytosis of a few specific proteins. How increased AMPK activity globally regulates the cell surface proteome is not known. I have developed a method to isolate the cell surface proteome from cultured cells. Coupling this method to quantitative mass spectrometry has allowed systematic identification of changes in the cell-surface proteome upon metabolic regulation. I found that activation of AMPK results in robust changes in the cell surface proteome, including cell adhesion and migration proteins. I confirmed that AMPK activation elicits a decrease in the cell surface abundance of the adhesion and migration protein β1-integrin, and that this is correlated with altered function of the endocytosis protein Dab2. Thus, my research furthers our understanding of how AMPK regulates the cell surface proteome and the specific mechanism by which AMPK regulates cellular adhesion and migration.

Abstract 13103: A Novel Anchor Protein TUG Mediates GLUT4 Translocation by AMP-activated Protein Kinase in the Ischemic Heart

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yina Ma ◽  
Wanqing Sun ◽  
Nanhu Quan ◽  
Lin Wang ◽  
Xingchi Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Glucose Uptake ◽  
Ex Vivo ◽  
Ischemic Heart ◽  
Ischemia And Reperfusion ◽  
Ampk Activation ◽  
Glut4 Translocation ◽  
Heart Perfusion ◽  
Amp Activated Protein Kinase

Introduction: Ischemic heart disease is a leading cause of death, and it is caused by reduced blood flow to the ischemic area. Thus, an increasing nutrient uptake is a key approach to increase cardiomyocyte survival rate during the ischemia and reperfusion (I/R) period. TUG (tether containing a UBX domain, for GLUT4, 60 KDa) is a regulator of GLUT4 trafficking, it can be cleaved to mobilize GLUT4 from intracellular membranes to the cell surface after insulin stimulation in skeletal muscle. The energy sensor AMP-activated protein kinase (AMPK) is known to play an important cardioprotective role during myocardial I/R by regulating GLUT4 translocation and glucose uptake. Hypothesis: TUG is one of the downstream targets of AMPK, which can be phosphorylated by hypoxia/ischemia induced AMPK activation. Phosphorylation of TUG accelerates its cleavage and increases GLUT4 translocation during ischemia/reperfusion in the heart. Methods: In vitro hypoxia chamber and ex vivo isolated mouse heart perfusion Langendorff system were used to test the hypothesis. Antithrombin (AT) is an endogenous AMPK agonist in the heart, which was used to define the role of TUG in regulating GLUT4 trafficking during ischemia and reperfusion in the heart. Results: The ex vivo heart perfusion data demonstrated that AT triggered AMPK activation and significantly increase glucose uptake and GLUT4 translocation during ischemia and reperfusion (p<0.05 vs. vehicle). Intriguingly, GLUT4 immunoprecipitation data showed that AT treatment caused a dissociation of TUG from GLUT4. Moreover, AT treatment increased abundance of a TUG cleavage product (42 KDa) in response to I/R. All of these glucose transporter trafficking events are blunted in the AMPK kinase dead (KD) transgenic hearts. In HL-1 cardiomyocytes, TUG proteins were phosphorylated by activated AMPK during hypoxia. Moreover, TUG siRNA knockdown the TUG of HL-1 cells caused significantly increased cell surface GLUT4 and glucose uptake. Conclusions: Cardiac AMPK activation stimulates TUG cleavage and causes the dissociation between TUG and GLUT4 in the intracellular vesicles. TUG is a critical mediator that modulates cardiac GLUT4 translocation to cell surface and enhances glucose uptake by AMPK signaling pathway.

scholarly journals The regulation of the cell surface proteome by amp-activated protein kinase

2021 ◽  
Author(s):  
Eden Ross
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Metabolic Regulation ◽  
Cultured Cells ◽  
Cellular Adhesion ◽  
Ampk Activation ◽  
And Migration ◽  
Surface Proteome ◽  
Amp Activated Protein Kinase ◽  
Cell Surface Proteome

The cell-surface proteome controls numerous cellular functions and is dynamically controlled by endocytosis and recycling under different cellular conditions. Energy stress is a state in which a cell must engage adaptive responses to ensure survival, including remodelling of the cell-surface proteome. AMP-activated protein kinase (AMPK) is an important metabolic regulator in the cell. Recent studies suggest AMPK activation may alter the endocytosis of a few specific proteins. How increased AMPK activity globally regulates the cell surface proteome is not known. I have developed a method to isolate the cell surface proteome from cultured cells. Coupling this method to quantitative mass spectrometry has allowed systematic identification of changes in the cell-surface proteome upon metabolic regulation. I found that activation of AMPK results in robust changes in the cell surface proteome, including cell adhesion and migration proteins. I confirmed that AMPK activation elicits a decrease in the cell surface abundance of the adhesion and migration protein β1-integrin, and that this is correlated with altered function of the endocytosis protein Dab2. Thus, my research furthers our understanding of how AMPK regulates the cell surface proteome and the specific mechanism by which AMPK regulates cellular adhesion and migration.

scholarly journals AMP-Activated Protein Kinase Regulates the Cell Surface Proteome and Integrin Membrane Traffic

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0128013 ◽  
Author(s):  
Eden Ross ◽  
Rehman Ata ◽  
Thanusi Thavarajah ◽  
Sergei Medvedev ◽  
Peter Bowden ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Membrane Traffic ◽  
Surface Proteome ◽  
Amp Activated Protein Kinase ◽  
Cell Surface Proteome

scholarly journals 0358: Differential AMP-activated protein kinase (AMPK) activation in platelets, in response to various agonists. Comparison between human and murine platelets

2014 ◽  
Vol 6 ◽  
pp. 57
Author(s):  
Sophie Lepropre ◽  
Marie-Blanche Onselaer ◽  
Cécile Oury ◽  
Luc Bertrand ◽  
Jean-Louis Vanoverschelde ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ampk Activation ◽  
Amp Activated Protein Kinase

AMPK activation with AICAR provokes an acute fall in plasma [K+]

2008 ◽  
Vol 294 (1) ◽  
pp. C126-C135 ◽  
Author(s):  
Dan Zheng ◽  
Anjana Perianayagam ◽  
Donna H. Lee ◽  
M. Douglas Brannan ◽  
Li E. Yang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infusion Rate ◽  
Extracellular Fluid ◽  
Ampk Activation ◽  
Conscious Rats ◽  
Significant Fall ◽  
Ampk Phosphorylation ◽  
Atp Levels ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K+ homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg/kg bolus then 4 mg·kg−1·min−1 infusion. Plasma [K+] and [glucose] both dropped at 1 h of AICAR infusion and [K+] dropped to 3.3 ± 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K+ excretion. AICAR lowered [K+] whether plasma [K+] was chronically elevated or lowered. The K+ infusion rate needed to maintain baseline plasma [K+] reached 15.7 ± 1.3 μmol K+·kg−1·min−1 between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K+] was not different from controls (4.2 ± 0.1 mM), but the fall in plasma [K+] in response to AICAR (0.25 g/kg) was blunted: [K+] fell to 3.6 ± 0.1 in controls and to 3.9 ± 0.1 mM in Tg-KD1, suggesting that ECF K+ redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K+] and suggest a novel mechanism for redistributing K+ from ECF to ICF.

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