Role of AMP-activated protein kinase in mechanism of metformin action.

PubWeight™: 23.21‹?› | Rank: Top 0.01% | All-Time Top 10000

🔗 View Article (PMC 209533)

Published in J Clin Invest on October 01, 2001


G Zhou1, R Myers, Y Li, Y Chen, X Shen, J Fenyk-Melody, M Wu, J Ventre, T Doebber, N Fujii, N Musi, M F Hirshman, L J Goodyear, D E Moller

Author Affiliations

1: Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

Associated clinical trials:

Study of Metformin With Simvastatin for Men With Prostate Carcinoma | NCT01561482

A Randomized, Placebo-controlled, Double-blind Phase II Study Evaluating if Glucophage Can Avoid Liver Injury Due to Chemotherapy Associated Steatosis (G-LUCAS) | NCT01523639

Adipokines in Obese Adolescents With Insulin Resistance | NCT01410604

The RCT of Acupuncture on PCOS Combined With IR | NCT02491333

Saxagliptin and Acute Myocardial Infarction:Effects on Platelet Function | NCT02377388

Efficacy Study of Pioglitazone and Metformin and Association Between Pioglitazone Response and Peroxisome Proliferator-activated Receptor Gamma Gene Variants in Bangladeshi Type 2 Diabetes Mellitus Subjects (T2DMCT) | NCT01589445

Metformin Pharmacology in Human Cancers: A Proof of Principle Study | NCT03477162

Articles citing this

(truncated to the top 100)

SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest (2002) 21.08

Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy (2012) 20.08

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol (2011) 15.71

Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol (2003) 12.91

The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science (2005) 12.35

The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A (2004) 12.30

LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J (2004) 10.82

AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature (2009) 10.59

AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol (2012) 10.42

Molecular mediators of hepatic steatosis and liver injury. J Clin Invest (2004) 9.40

Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes (2009) 8.70

The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer (2009) 8.43

AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A (2007) 8.23

Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol (2007) 8.08

The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A (2005) 7.38

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy (2016) 7.05

p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell (2008) 6.88

The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol (2011) 6.83

New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care (2009) 6.17

The Concise Guide to PHARMACOLOGY 2013/14: enzymes. Br J Pharmacol (2013) 5.57

Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell (2008) 5.51

Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest (2010) 5.39

CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J Clin Invest (2004) 5.36

AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev (2011) 5.26

Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev (2004) 5.00

AMP-activated protein kinase--development of the energy sensor concept. J Physiol (2006) 4.93

Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci U S A (2003) 4.87

Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest (2007) 4.47

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet (2010) 4.42

Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci U S A (2002) 4.40

Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. EMBO J (2005) 4.31

SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J Biol Chem (2008) 4.16

Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab (2010) 4.14

The AMP-activated protein kinase alpha2 catalytic subunit controls whole-body insulin sensitivity. J Clin Invest (2003) 4.11

PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol (2009) 4.09

Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab (2010) 4.08

Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) (2012) 4.04

AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab (2011) 3.98

Metformin prevents tobacco carcinogen--induced lung tumorigenesis. Cancer Prev Res (Phila) (2010) 3.86

The ancient drug salicylate directly activates AMP-activated protein kinase. Science (2012) 3.77

Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature (2013) 3.76

Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature (2013) 3.72

Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol (2006) 3.67

Metformin prevents alcohol-induced liver injury in the mouse: Critical role of plasminogen activator inhibitor-1. Gastroenterology (2006) 3.53

An emerging role of mTOR in lipid biosynthesis. Curr Biol (2009) 3.50

AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest (2006) 3.39

Mitochondria--a nexus for aging, calorie restriction, and sirtuins? Cell (2008) 3.38

AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell Metab (2012) 3.35

AMPK and cell proliferation--AMPK as a therapeutic target for atherosclerosis and cancer. J Physiol (2006) 3.11

Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature (2014) 3.09

ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A (2010) 3.03

Chemical genetic screen for AMPKα2 substrates uncovers a network of proteins involved in mitosis. Mol Cell (2011) 2.99

LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol (Oxf) (2009) 2.94

Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS One (2010) 2.81

Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice. Diabetes (2011) 2.72

Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell (2009) 2.69

Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up. Arch Pediatr Adolesc Med (2010) 2.68

Metformin improves healthspan and lifespan in mice. Nat Commun (2013) 2.68

The promise and peril of chemical probes. Nat Chem Biol (2015) 2.64

AMP-activated protein kinase protects cardiomyocytes against hypoxic injury through attenuation of endoplasmic reticulum stress. Mol Cell Biol (2005) 2.56

The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis. Proc Natl Acad Sci U S A (2009) 2.55

Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem (2007) 2.54

Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors. Bioorg Med Chem Lett (2008) 2.51

Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc Natl Acad Sci U S A (2004) 2.48

Phosphorylation of LKB1 at serine 428 by protein kinase C-zeta is required for metformin-enhanced activation of the AMP-activated protein kinase in endothelial cells. Circulation (2008) 2.48

Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol (2006) 2.47

AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest (2013) 2.44

New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J (2002) 2.41

Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med (2014) 2.39

Metformin disrupts crosstalk between G protein-coupled receptor and insulin receptor signaling systems and inhibits pancreatic cancer growth. Cancer Res (2009) 2.36

Hematopoietic AMPK β1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest (2011) 2.34

In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS Chem Biol (2010) 2.29

The Concise Guide to PHARMACOLOGY 2013/14: catalytic receptors. Br J Pharmacol (2013) 2.29

Understanding the benefit of metformin use in cancer treatment. BMC Med (2011) 2.28

Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53. EMBO J (2007) 2.27

Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci U S A (2010) 2.27

Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol (2010) 2.26

Oral antihyperglycemic therapy for type 2 diabetes mellitus. CMAJ (2005) 2.24

BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions. Cell (2012) 2.20

Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res (2008) 2.19

Non-alcoholic fatty liver disease and the metabolic syndrome: an update. World J Gastroenterol (2008) 2.17

Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury. Am J Physiol Lung Cell Mol Physiol (2008) 2.15

Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest (2013) 2.14

AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Acta Physiol (Oxf) (2009) 2.13

AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol (2010) 2.11

Beneficial endocrine but adverse exocrine effects of sitagliptin in the human islet amyloid polypeptide transgenic rat model of type 2 diabetes: interactions with metformin. Diabetes (2009) 2.10

Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One (2013) 2.10

Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation (2009) 2.09

AMPK: Lessons from transgenic and knockout animals. Front Biosci (Landmark Ed) (2009) 2.09

Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer (2010) 2.04

AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte: potential mechanism and physiological relevance. J Biol Chem (2008) 2.02

Roles of 5'-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochem J (2003) 2.02

Metformin: multi-faceted protection against cancer. Oncotarget (2011) 2.00

Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care (2013) 1.99

Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS One (2008) 1.99

Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal (2008) 1.96

AMP-activated protein kinase and its downstream transcriptional pathways. Cell Mol Life Sci (2010) 1.95

Etoposide induces ATM-dependent mitochondrial biogenesis through AMPK activation. PLoS One (2008) 1.94

Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr (2009) 1.94

Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner. J Cell Mol Med (2011) 1.93

Articles cited by this

Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J (2000) 7.77

The AMP-activated protein kinase--fuel gauge of the mammalian cell? Eur J Biochem (1997) 7.69

Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem (2000) 6.86

What if Minkowski had been ageusic? An alternative angle on diabetes. Science (1992) 6.07

The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem (1997) 6.04

Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell (2000) 5.92

AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol (1997) 5.74

Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med (2000) 5.13

Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes (2000) 4.80

Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay. Eur J Biochem (1989) 4.65

AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol (1999) 4.58

Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver. Proc Natl Acad Sci U S A (1995) 4.40

Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes (1998) 4.31

Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med (1995) 4.29

Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes (2000) 3.23

Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle. J Appl Physiol (1985) (1999) 3.14

Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem (1989) 3.09

Accumulation of metformin by tissues of the normal and diabetic mouse. Xenobiotica (1994) 2.94

Cellular mechanism of metformin action involves glucose transporter translocation from an intracellular pool to the plasma membrane in L6 muscle cells. Endocrinology (1992) 2.94

Metformin: a review of its pharmacological properties and therapeutic use. Diabete Metab (1979) 2.89

Mitochondrial and peroxisomal fatty acid oxidation in liver homogenates and isolated hepatocytes from control and clofibrate-treated rats. J Biol Chem (1979) 2.66

5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. Diabetes (2000) 2.39

AMP-activated protein kinase inhibits the glucose-activated expression of fatty acid synthase gene in rat hepatocytes. J Biol Chem (1998) 2.38

Diurnal rhythm of phosphorylation of rat liver acetyl-CoA carboxylase by the AMP-activated protein kinase, demonstrated using freeze-clamping. Effects of high fat diets. Eur J Biochem (1992) 2.27

Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'-AMP-activated protein kinase. J Biol Chem (1992) 2.22

Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets. Proc Natl Acad Sci U S A (2000) 2.11

The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs (1999) 1.94

Effect of metformin on carbohydrate and lipoprotein metabolism in NIDDM patients. Diabetes Care (1990) 1.90

Biguanides. A review of history, pharmacodynamics and therapy. Diabete Metab (1983) 1.83

The effect of intravenous metformin on glucose metabolism during hyperglycaemia in type 2 diabetes. Diabet Med (1992) 1.73

Subcellular distribution of metformin in rat liver. J Pharm Pharmacol (1991) 1.50

Membrane physiology as a basis for the cellular effects of metformin in insulin resistance and diabetes. Diabetes Metab (1999) 1.49

AMP-activated protein kinase: a critical signaling intermediary for exercise-stimulated glucose transport? Exerc Sport Sci Rev (2000) 1.43

Effect of metformin on insulin-stimulated glucose transport in isolated skeletal muscle obtained from patients with NIDDM. Diabetologia (1994) 1.42

Articles by these authors

The sequence of the human genome. Science (2001) 101.55

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature (2000) 47.15

The Ensembl genome database project. Nucleic Acids Res (2002) 40.87

Gene-expression profiles in hereditary breast cancer. N Engl J Med (2001) 29.80

Ensembl 2009. Nucleic Acids Res (2008) 25.38

SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields. J Struct Biol (1996) 22.89

Ensembl 2008. Nucleic Acids Res (2007) 20.67

Ensembl 2007. Nucleic Acids Res (2006) 20.10

A protein interaction map of Drosophila melanogaster. Science (2003) 20.06

Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet (1996) 15.73

Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature (2000) 15.53

Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature (1997) 15.49

Ensembl 2005. Nucleic Acids Res (2005) 15.13

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy (2008) 12.35

Ensembl 2002: accommodating comparative genomics. Nucleic Acids Res (2003) 12.26

Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell (2000) 11.90

Ensembl 2004. Nucleic Acids Res (2004) 11.88

Ensembl 2006. Nucleic Acids Res (2006) 11.66

Expression profiling using cDNA microarrays. Nat Genet (1999) 11.58

Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes. Nature (1999) 10.97

A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet (1997) 10.93

Regulation of simian virus 40 early transcription in vitro by a purified tumor antigen. Proc Natl Acad Sci U S A (1980) 10.22

Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem (1999) 10.14

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci U S A (2006) 9.26

Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell (1992) 9.19

The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell (2000) 8.95

Data management and analysis for gene expression arrays. Nat Genet (1998) 8.60

A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell (1994) 8.44

Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns. Cancer Res (2001) 8.34

Ratio-based decisions and the quantitative analysis of cDNA microarray images. J Biomed Opt (1997) 8.32

A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell (1998) 8.10

Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science (2001) 7.66

LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature (2001) 7.44

Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science (1997) 7.31

Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes (1999) 7.14

The genome of the natural genetic engineer Agrobacterium tumefaciens C58. Science (2001) 6.90

An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem (1999) 6.88

Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke (2001) 6.61

MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene (2007) 6.55

Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat Genet (1993) 6.53

Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science (1997) 6.23

RSC, an essential, abundant chromatin-remodeling complex. Cell (1996) 6.17

Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science (1997) 6.00

BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science (1999) 5.99

Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. Science (1999) 5.95

The evolution of H5N1 influenza viruses in ducks in southern China. Proc Natl Acad Sci U S A (2004) 5.87

A simple method for clinical assay of superoxide dismutase. Clin Chem (1988) 5.66

Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell (1998) 5.60

Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A (2001) 5.48

CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature (1997) 5.45

Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum (2001) 5.36

Genetic diversity and disease control in rice. Nature (2000) 5.34

Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J (1998) 5.34

Tumor induction of VEGF promoter activity in stromal cells. Cell (1998) 5.20

Macrophage tropism determinants of human immunodeficiency virus type 1 in vivo. J Virol (1992) 5.19

Spin-torque switching with the giant spin Hall effect of tantalum. Science (2012) 5.18

Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA (1998) 5.09

A candidate prostate cancer susceptibility gene at chromosome 17p. Nat Genet (2001) 5.06

Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody. Proc Natl Acad Sci U S A (1996) 5.04

Extensive variation of human immunodeficiency virus type-1 in vivo. Nature (1988) 5.02

Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Euro Surveill (2012) 4.96

Cross-bridge model of muscle contraction. Quantitative analysis. Biophys J (1980) 4.91

A simple colorimetric method for determination of protein. Anal Biochem (1969) 4.87

Area V5 of the human brain: evidence from a combined study using positron emission tomography and magnetic resonance imaging. Cereb Cortex (1993) 4.79

Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood (1997) 4.78

Reducing obesity and related chronic disease risk in children and youth: a synthesis of evidence with 'best practice' recommendations. Obes Rev (2006) 4.74

Prevention of fat-induced insulin resistance by salicylate. J Clin Invest (2001) 4.74

Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays. Cancer Res (1998) 4.68

Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat Genet (1998) 4.67

Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature (2000) 4.66

Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke (2001) 4.64

Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. Proc Natl Acad Sci U S A (1995) 4.54

Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. Cancer Res (2001) 4.51

Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol Cell (1999) 4.49

Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat Genet (2001) 4.48

Femtosecond electronic response of atoms to ultra-intense X-rays. Nature (2010) 4.46

MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene (2008) 4.43

Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport. Diabetes (1998) 4.31

Growth suppression by p18, a p16INK4/MTS1- and p14INK4B/MTS2-related CDK6 inhibitor, correlates with wild-type pRb function. Genes Dev (1994) 4.30

The coxsackievirus-adenovirus receptor protein can function as a cellular attachment protein for adenovirus serotypes from subgroups A, C, D, E, and F. J Virol (1998) 4.26

UmuD'(2)C is an error-prone DNA polymerase, Escherichia coli pol V. Proc Natl Acad Sci U S A (1999) 4.24

Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac. J Virol (1988) 4.24

Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res (1999) 4.20

Cell cycle dynamics of an M-phase-specific cytoplasmic factor in Xenopus laevis oocytes and eggs. J Cell Biol (1984) 4.20

Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr Biol (2001) 4.16

Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology (1998) 4.13

A viral phospholipase A2 is required for parvovirus infectivity. Dev Cell (2001) 3.97

Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science (1994) 3.96

Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis. Nature (2000) 3.95

Mechanism of insulin resistance in A-ZIP/F-1 fatless mice. J Biol Chem (2000) 3.90

Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry (2001) 3.87

Comparative genomic hybridization analysis of 38 breast cancer cell lines: a basis for interpreting complementary DNA microarray data. Cancer Res (2000) 3.83

Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function. Dev Biol (2001) 3.82

A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. Mol Cell (1999) 3.80

Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest (2001) 3.79

Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J Clin Invest (2000) 3.78

Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet (2000) 3.72

Actin-dependent propulsion of endosomes and lysosomes by recruitment of N-WASP. J Cell Biol (2000) 3.71

The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia (2008) 3.69