Anton Bennett, PhD
Research & Publications
Biography
News
Research Summary
Protein tyrosine phosphorylation mediates numerous fundamental physiological events such as mitogenesis, differentiation, cell movement and apoptosis. Our laboratory is interested in how protein tyrosine phosphatases (PTPs) participate in the regulation of these cellular processes. In order to decipher how PTPs regulate mammalian cell signaling we use a broad range of approaches from molecular biology to mouse genetic strategies.
The ultimate goal of our research on protein tyrosine phosphatases is to establish whether the PTPs participate in disease processes such as cancer, cardiovascular disease, diabetes and rare diseases such as muscular dystrophy. Our long-term research goals are to identify novel mechanisms of PTP regulation in disease and to leverage this information to determine whether inhibiting these enzymes might serve as novel therapeutic targets for the treatment of human diseases.
For further information please visit the Bennett Lab website - Home | Bennett Lab (bennett-lab.org)
Extensive Research Description
Cell proliferation, cell differentiation and death are controlled by signaling pathways that are mediated by protein tyrosyl phosphorylation. The net cellular level of protein tyrosyl phosphorylation is regulated by the intrinsic and opposing activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Dysregulation of the net level of tyrosyl phosphorylation causes cancer, diabetes, cardiovascular disease and developmental abnormalities.
We focus our studies on how PTPs regulate cell signaling by controlling protein tyrosyl dephosphorylation. We are also exploring how PTPs participate in the pathogenesis of diseases such as obesity and diabetes, cardiovascular disease and developmental abnormalities. These research efforts are being accomplished by using integrated approaches that encompass cell biology, genetics, protein biochemistry, cell imaging and animal models. Our long-term research goals are to uncover the function of PTPs in order to identify whether these enzymes might serve as novel therapeutic targets for the treatment of human diseases.
For further information please visit the Bennett Lab website - Home | Bennett Lab (bennett-lab.org)
Coauthors
Research Interests
Cardiovascular Diseases; Musculoskeletal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurosciences; Nutritional and Metabolic Diseases; Signal Transduction
Selected Publications
- Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?Shillingford S, Bennett A. Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable? The Annual Review Of Pharmacology And Toxicology 2023, 63: 617-636. PMID: 36662585, DOI: 10.1146/annurev-pharmtox-051921-121923.
- Abstract 225: Lack Of Map Kinase Phosphatase-5 In Macrophages Protects Ldlr-null Mice Against AtherogenesisZhang X, Zhao Z, Baldini M, Zhang C, Tao B, Zhang L, Bennett A, Yu J. Abstract 225: Lack Of Map Kinase Phosphatase-5 In Macrophages Protects Ldlr-null Mice Against Atherogenesis Arteriosclerosis Thrombosis And Vascular Biology 2022, 42: a225-a225. DOI: 10.1161/atvb.42.suppl_1.225.
- Abstract 16205: MKP-5 Deficiency Attenuates Pressure Overload-induced Cardiac HypertrophyMin K, Huang Y, Giordano F, Bajpeyi S, Bennett A. Abstract 16205: MKP-5 Deficiency Attenuates Pressure Overload-induced Cardiac Hypertrophy Circulation 2020, 142 DOI: 10.1161/circ.142.suppl_3.16205.
- SH2 domain-containing Phosphatase-(SHP)-2 blunts fibrotic responses through regulation of fibroblast mitochondrial metabolism and autophagyTzouvelekis A, Yu G, Ahangari F, Bennett A, Karampitsakos T, Bouros D, Bouros E, Kaminski N. SH2 domain-containing Phosphatase-(SHP)-2 blunts fibrotic responses through regulation of fibroblast mitochondrial metabolism and autophagy 2019, pa583. DOI: 10.1183/13993003.congress-2019.pa583.
- Role of Mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosisTzouvelekis A, Karampitsakos T, Min K, Xylourgidis N, Yu G, Herazo-Maya J, Bizenhofer L, Bennett A, Kaminski N. Role of Mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosis 2018, lsc-1111. DOI: 10.1183/13993003.congress-2018.lsc-1111.
- MKP-5 inhibition blunts fibrotic responses in-vitro and in-vivo through negative regulation of TGFB1-induced smad3-signallingTzouvelekis A, Xylourgidis N, Min K, Karampitsakos T, Ninou I, Barbayianni I, Bennett A, Aidinis V, Kaminski N. MKP-5 inhibition blunts fibrotic responses in-vitro and in-vivo through negative regulation of TGFB1-induced smad3-signalling 2018, oa5350. DOI: 10.1183/13993003.congress-2018.oa5350.
- MKP-5 Establishes Skeletal Muscle Metabolic Quiescence by Negatively Regulating MAPK-dependent Mitochondrial FunctionMin K, Bennett A. MKP-5 Establishes Skeletal Muscle Metabolic Quiescence by Negatively Regulating MAPK-dependent Mitochondrial Function Medicine & Science In Sports & Exercise 2017, 49: 98. DOI: 10.1249/01.mss.0000517094.23230.9d.
- Low-dose dasatinib rescues cardiac function in Noonan syndromeYi JS, Huang Y, Kwaczala AT, Kuo IY, Ehrlich BE, Campbell SG, Giordano FJ, Bennett AM. Low-dose dasatinib rescues cardiac function in Noonan syndrome JCI Insight 2016, 1: e90220. PMID: 27942593, PMCID: PMC5135272, DOI: 10.1172/jci.insight.90220.
- SH2 domain-containing phosphatase-SHP-2 is a novel anti-fibrotic regulator in pulmonary fibrosisTzouvelekis A, Yu G, Herazo-Maya J, Woolard T, Zhang Y, Lee H, Lee P, Herzog E, Bennett A, Kaminski N. SH2 domain-containing phosphatase-SHP-2 is a novel anti-fibrotic regulator in pulmonary fibrosis 2016, oa4979. DOI: 10.1183/13993003.congress-2016.oa4979.
- Mining the function of protein tyrosine phosphatases in health and diseaseLee H, Yi JS, Lawan A, Min K, Bennett AM. Mining the function of protein tyrosine phosphatases in health and disease Seminars In Cell And Developmental Biology 2014, 37: 66-72. PMID: 25263013, PMCID: PMC4339398, DOI: 10.1016/j.semcdb.2014.09.021.
- Mitogen-Activated Protein Kinase Phosphatases in MetabolismLawan A, Bennett A. Mitogen-Activated Protein Kinase Phosphatases in Metabolism 2013, 221-238. DOI: 10.1007/978-1-4614-7855-3_12.
- Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5Shi H, Verma M, Zhang L, Dong C, Flavell RA, Bennett AM. Improved regenerative myogenesis and muscular dystrophy in mice lacking Mkp5 Journal Of Clinical Investigation 2013, 123: 2064-2077. PMID: 23543058, PMCID: PMC3635719, DOI: 10.1172/jci64375.
- Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesityDiano S, Liu Z, Jeong J, Dietrich M, Ruan H, Kim E, Suyama S, Kelly K, Gyengesi E, Arbiser J, Belsham D, Sarruf D, Schwartz M, Bennett A, Shanabrough M, Mobbs C, Yang X, Gao X, Horvath T. Erratum: Corrigendum: Peroxisome proliferation–associated control of reactive oxygen species sets melanocortin tone and feeding in diet-induced obesity Nature Medicine 2011, 17: 1320-1320. DOI: 10.1038/nm1011-1320a.
- Loss of Mitogen-activated Protein Kinase Phosphatase-1 Protects from Hepatic Steatosis by Repression of Cell Death-inducing DNA Fragmentation Factor A (DFFA)-like Effector C (CIDEC)/Fat-specific Protein 27*Flach RJ, Qin H, Zhang L, Bennett AM. Loss of Mitogen-activated Protein Kinase Phosphatase-1 Protects from Hepatic Steatosis by Repression of Cell Death-inducing DNA Fragmentation Factor A (DFFA)-like Effector C (CIDEC)/Fat-specific Protein 27* Journal Of Biological Chemistry 2011, 286: 22195-22202. PMID: 21521693, PMCID: PMC3121364, DOI: 10.1074/jbc.m110.210237.
- Chapter 92 Approaches to the Identification of Protein Tyrosine Phosphatase SubstratesBennett A, Tiganis T. Chapter 92 Approaches to the Identification of Protein Tyrosine Phosphatase Substrates 2010, 717-725. DOI: 10.1016/b978-0-12-374145-5.00092-9.
- MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in miceRoth RJ, Le AM, Zhang L, Kahn M, Samuel VT, Shulman GI, Bennett AM. MAPK phosphatase-1 facilitates the loss of oxidative myofibers associated with obesity in mice Journal Of Clinical Investigation 2009, 119: 3817-3829. PMID: 19920356, PMCID: PMC2786792, DOI: 10.1172/jci39054.
- Mitogen-activated protein kinase phosphatase-1 (MKP-1): a critical regulator of innate immune responsesChi H, Bennett A, Flavell R. Mitogen-activated protein kinase phosphatase-1 (MKP-1): a critical regulator of innate immune responses Journal Of Organ Dysfunction 2007, 3: 72-81. DOI: 10.1080/17471060601137415.
- Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminusChauvet V, Tian X, Husson H, Grimm D, Wang T, Hieseberger T, Igarashi P, Bennett A, Ibraghimov-Beskrovnaya O, Somlo S, Caplan M. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus Journal Of Clinical Investigation 2005, 115: 788-788. DOI: 10.1172/jci21753c1.
- SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis.Kontaridis M, Liu X, Zhang L, Bennett A. SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis. Journal Of Cell Science 2001, 114: 2187-98. PMID: 11493654, DOI: 10.1242/jcs.114.11.2187.
- Differential Role of β1C and β1AIntegrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase PathwaysFornaro M, Steger C, Bennett A, Wu J, Languino L. Differential Role of β1C and β1AIntegrin Cytoplasmic Variants in Modulating Focal Adhesion Kinase, Protein Kinase B/AKT, and Ras/Mitogen-activated Protein Kinase Pathways Molecular Biology Of The Cell 2000, 11: 2235-2249. PMID: 10888665, PMCID: PMC14916, DOI: 10.1091/mbc.11.7.2235.
- Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine PhosphataseTiganis T, Bennett A, Ravichandran K, Tonks N. Epidermal Growth Factor Receptor and the Adaptor Protein p52Shc Are Specific Substrates of T-Cell Protein Tyrosine Phosphatase Molecular And Cellular Biology 1998, 18: 1622-1634. PMID: 9488479, PMCID: PMC108877, DOI: 10.1128/mcb.18.3.1622.
- Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein KinasesBennett A, Tonks N. Regulation of Distinct Stages of Skeletal Muscle Differentiation by Mitogen-Activated Protein Kinases Science 1997, 278: 1288-1291. PMID: 9360925, DOI: 10.1126/science.278.5341.1288.
- Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression.Bennett A, Hausdorff S, O'Reilly A, Freeman R, Neel B. Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression. Molecular And Cellular Biology 1996, 16: 1189-1202. PMID: 8622663, PMCID: PMC231101, DOI: 10.1128/mcb.16.3.1189.
- Different Signaling Roles of SHPTP2 in Insulin-induced GLUT1 Expression and GLUT4 Translocation ∗Hausdorff S, Bennett A, Neel B, Birnbaum M. Different Signaling Roles of SHPTP2 in Insulin-induced GLUT1 Expression and GLUT4 Translocation ∗ Journal Of Biological Chemistry 1995, 270: 12965-12968. PMID: 7768884, DOI: 10.1074/jbc.270.22.12965.
- Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras.Bennett A, Tang T, Sugimoto S, Walsh C, Neel B. Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 7335-7339. PMID: 8041791, PMCID: PMC44394, DOI: 10.1073/pnas.91.15.7335.
- Calcium as a permissive factor but not an initiation factor in DNA synthesis induction in cultured rat hepatocytes by the peroxisome proliferator ciprofibrateBennett A, Williams G. Calcium as a permissive factor but not an initiation factor in DNA synthesis induction in cultured rat hepatocytes by the peroxisome proliferator ciprofibrate Biochemical Pharmacology 1993, 46: 2219-2227. PMID: 8274155, DOI: 10.1016/0006-2952(93)90612-z.
- Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor.Lechleider R, Sugimoto S, Bennett A, Kashishian A, Cooper J, Shoelson S, Walsh C, Neel B. Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor. Journal Of Biological Chemistry 1993, 268: 21478-21481. PMID: 7691811, DOI: 10.1016/s0021-9258(20)80562-6.
- Alteration of rat liver endoplasmic reticulum Ca2+-ATPase thiol integrity by ciprofibrate, a peroxisome proliferatorBennett A, Williams G. Alteration of rat liver endoplasmic reticulum Ca2+-ATPase thiol integrity by ciprofibrate, a peroxisome proliferator Biochemical Pharmacology 1993, 45: 2093-2098. PMID: 8512590, DOI: 10.1016/0006-2952(93)90021-n.
- Studies on the Effects of Peroxisome Proliferators as Novel Ca2+ Mobilizing Agents Using Indo-1-Loaded HepatocytesBennett A, Flint O, Williams G. Studies on the Effects of Peroxisome Proliferators as Novel Ca2+ Mobilizing Agents Using Indo-1-Loaded Hepatocytes 1993, 143-151. DOI: 10.1007/978-1-4615-2828-9_17.
- Reduction of rat liver endoplasmic reticulum Ca2+-ATPase activity and mobilization of hepatic intracellular calcium by ciprofibrate, a peroxisome proliferatorBennett A, Williams G. Reduction of rat liver endoplasmic reticulum Ca2+-ATPase activity and mobilization of hepatic intracellular calcium by ciprofibrate, a peroxisome proliferator Biochemical Pharmacology 1992, 43: 595-605. PMID: 1531754, DOI: 10.1016/0006-2952(92)90583-5.