Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression

Neurosignals, Journal Year: 2012, Volume and Issue: 21(1-2), P. 28 - 41

Published: March 28, 2012

Despite an alarming increase in the burden of obesity worldwide, body adiposity seems to be a regulated physiological variable. Regulation occurs through classical endocrine feedback loop, which pancreatic beta-cell-derived hormone insulin and adipocyte-derived leptin signal status energy stores hypothalamus. Recent advances our understanding transduction mechanisms used by hypothalamus modulate neuronal firing suggest that intracellular cross-talk at several levels is potentially important determinant weight. These pathways are thus attractive target for pharmacological intervention treatment obesity.

Language: Английский

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The ground state of embryonic stem cell self-renewal

Nature, Journal Year: 2008, Volume and Issue: 453(7194), P. 519 - 523

Published: May 1, 2008

Language: Английский

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Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

Microbiology and Molecular Biology Reviews, Journal Year: 2011, Volume and Issue: 75(1), P. 50 - 83

Published: March 1, 2011

SUMMARY The mitogen-activated protein kinases (MAPKs) regulate diverse cellular programs by relaying extracellular signals to intracellular responses. In mammals, there are more than a dozen MAPK enzymes that coordinately cell proliferation, differentiation, motility, and survival. best known the conventional MAPKs, which include signal-regulated 1 2 (ERK1/2), c-Jun amino-terminal 3 (JNK1 -3), p38 (α, β, γ, δ), ERK5 families. There additional, atypical enzymes, including ERK3/4, ERK7/8, Nemo-like kinase (NLK), have distinct regulation functions. Together, MAPKs large number of substrates, members family Ser/Thr termed MAPK-activated (MAPKAPKs). MAPKAPKs related respond stimulation through direct MAPK-dependent activation loop phosphorylation activation. five MAPKAPK subfamilies: p90 ribosomal S6 (RSK), mitogen- stress-activated (MSK), MAPK-interacting (MNK), 2/3 (MK2/3), MK5 (also as p38-regulated/activated [PRAK]). These biological functions, nucleosome gene expression, mRNA stability translation, proliferation Here we review mechanisms different discuss their physiological roles based on established substrates recent discoveries.

Language: Английский

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Targeting cancer with small molecule kinase inhibitors

Nature reviews. Cancer, Journal Year: 2008, Volume and Issue: 9(1), P. 28 - 39

Published: Dec. 19, 2008

Language: Английский

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Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update

Physiological Reviews, Journal Year: 2012, Volume and Issue: 92(2), P. 689 - 737

Published: April 1, 2012

The mammalian stress-activated families of mitogen-activated protein kinases (MAPKs) were first elucidated in 1994, and by 2001, substantial progress had been made identifying the architecture pathways upstream these as well cataloguing candidate substrates. This information remains largely sound. Nevertheless, an informed understanding physiological pathophysiological roles remained to be accomplished. In past decade, there has explosion new work using RNAi cells, transgenic, knockout conditional technology mice that provided valuable insight into functions MAPK pathways. These findings have important implications our organ development, innate acquired immunity, diseases such atherosclerosis, tumorigenesis, type 2 diabetes. developments bring us within striking distance development validation novel treatment strategies. Herein we summarize molecular components stress-regulated their regulation described thus far. We then review some vivo

Language: Английский

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Exercise, GLUT4, and Skeletal Muscle Glucose Uptake

Physiological Reviews, Journal Year: 2013, Volume and Issue: 93(3), P. 993 - 1017

Published: July 1, 2013

Glucose is an important fuel for contracting muscle, and normal glucose metabolism vital health. enters the muscle cell via facilitated diffusion through GLUT4 transporter which translocates from intracellular storage depots to plasma membrane T-tubules upon contraction. Here we discuss current understanding of how exercise-induced uptake regulated. We briefly role supply concentrate on translocation molecular signaling that sets this in motion during contractions. Contraction-induced complex involves a variety molecules including AMPK, Ca 2+ , NOS proximal part cascade as well GTPases, Rab, SNARE proteins cytoskeletal components distal part. While acute regulation relies translocation, also depends expression increased following exercise. AMPK CaMKII are key kinases appear regulate HDAC4/5-MEF2 axis MEF2-GEF interactions resulting nuclear export HDAC4/5 turn leading histone hyperacetylation promoter transcription. Exercise training most potent stimulus increase skeletal expression, effect may partly contribute improved insulin action disposal enhanced glycogen exercise health disease.

Language: Английский

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Akt signalling in health and disease

Cellular Signalling, Journal Year: 2011, Volume and Issue: 23(10), P. 1515 - 1527

Published: May 22, 2011

Language: Английский

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Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

Nature Biotechnology, Journal Year: 2011, Volume and Issue: 29(11), P. 1039 - 1045

Published: Oct. 30, 2011

Language: Английский

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Ligand-Independent HER2/HER3/PI3K Complex Is Disrupted by Trastuzumab and Is Effectively Inhibited by the PI3K Inhibitor GDC-0941

Cancer Cell, Journal Year: 2009, Volume and Issue: 15(5), P. 429 - 440

Published: May 1, 2009

Language: Английский

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Capture of Authentic Embryonic Stem Cells from Rat Blastocysts

Cell, Journal Year: 2008, Volume and Issue: 135(7), P. 1287 - 1298

Published: Dec. 1, 2008

Language: Английский

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