Genomes and Genes
Gene Symbol: Ptpn11
Description: protein tyrosine phosphatase, non-receptor type 11
Alias: Shp2, tyrosine-protein phosphatase non-receptor type 11, PTP-1D, SH-PTP2 protein tyrosine phosphatase, non-receptor type 11, SHP-2, encodes catalytic domain, protein tyrosine phosphatase SH-PTP2, protein-tyrosine phosphatase 1D, protein-tyrosine phosphatase SYP
- Tabet F, Schiffrin E, Callera G, He Y, Yao G, Ostman A, et al. Redox-sensitive signaling by angiotensin II involves oxidative inactivation and blunted phosphorylation of protein tyrosine phosphatase SHP-2 in vascular smooth muscle cells from SHR. Circ Res. 2008;103:149-58 pubmed publisher..We identify a novel redox-sensitive SHP-2-dependent pathway for Ang II in VSMCs. SHP-2 dysregulation by increased Nox1-derived ROS in SHR is associated with altered Ang II-AKT signaling. ..
- Yuan L, Yu W, Qu C. DNA damage-induced G2/M checkpoint in SV40 large T antigen-immortalized embryonic fibroblast cells requires SHP-2 tyrosine phosphatase. J Biol Chem. 2003;278:42812-20 pubmed..These results together provide the first evidence that SHP-2 tyrosine phosphatase enhances the DNA damage G2/M checkpoint in SV40 large T antigen immortalized murine embryonic fibroblast cells. ..
- Hayashi K, Shibata K, Morita T, Iwasaki K, Watanabe M, Sobue K. Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cells. J Biol Chem. 2004;279:40807-18 pubmed
- Tolarová H, Dráberová L, Heneberg P, Draber P. Involvement of filamentous actin in setting the threshold for degranulation in mast cells. Eur J Immunol. 2004;34:1627-36 pubmed..The combined data suggest that actin polymerization is critical for setting the thresholds for mast cell signaling via aggregation of both Fc epsilon RI and GPI-anchored proteins. ..
- Gonçalves D, Marin T, Pereira M, Santos A, Paes Leme A, Franchini K. ?B-Crystallin interacts and attenuates the tyrosine phosphatase activity of Shp2 in cardiomyocytes under mechanical stress. FEBS Lett. 2016;590:2232-40 pubmed publisherThe small heat shock protein ?B-Crystallin (CryAB, HspB5) and SH2 domain-containing tyrosine phosphatase 2 (Shp2) are important molecules in heart response to pathophysiological stress...
- Araki T, Mohi M, Ismat F, Bronson R, Williams I, Kutok J, et al. Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation. Nat Med. 2004;10:849-57 pubmed..Mutations of Ptpn11 (also known as Shp2), which encodes the protein-tyrosine phosphatase Shp2, occur in approximately 50% of ..
- Nakaoka Y, Shioyama W, Kunimoto S, Arita Y, Higuchi K, Yamamoto K, et al. SHP2 mediates gp130-dependent cardiomyocyte hypertrophy via negative regulation of skeletal alpha-actin gene. J Mol Cell Cardiol. 2010;49:157-64 pubmed publisher..Here, we clarified the role of SH2-containing protein tyrosine phosphatase 2 (SHP2) in alpha-SKA gene expression...
- D Alessio A, Cerchia L, Amelio I, Incoronato M, Condorelli G, de Franciscis V. Shp2 in PC12 cells: NGF versus EGF signalling. Cell Signal. 2007;19:1193-200 pubmed..Here we focused on the cytosolic tyrosine phosphatase Shp2 as an established regulator of the Ras-ERK cascade, to elucidate its involvement in determining the stimulation-..
- Oh J, Rhee S, Silva A, Lee Y, Kim H. Noonan syndrome-associated SHP2 mutation differentially modulates the expression of postsynaptic receptors according to developmental maturation. Neurosci Lett. 2017;649:41-47 pubmed publisher..Previously, a Noonan syndrome (NS)-associated SHP2 mutation (SHP2D61G) was shown to increase the synaptic delivery of AMPA receptor, subsequently impairing ..
- Kolli S, Zito C, Mossink M, Wiemer E, Bennett A. The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal growth factor signaling. J Biol Chem. 2004;279:29374-85 pubmed..We propose that MVP functions as a novel scaffold protein for both SHP-2 and Erk. The regulation of MVP tyrosyl phosphorylation by SHP-2 may play an important role in cell survival signaling...
- Kontaridis M, Yang W, Bence K, Cullen D, Wang B, Bodyak N, et al. Deletion of Ptpn11 (Shp2) in cardiomyocytes causes dilated cardiomyopathy via effects on the extracellular signal-regulated kinase/mitogen-activated protein kinase and RhoA signaling pathways. Circulation. 2008;117:1423-35 pubmed publisher..Here, we show that mice with muscle-specific deletion of Ptpn11, the gene encoding the SH2 domain-containing PTP Shp2, rapidly develop a compensated dilated cardiomyopathy ..
- Jafarov T, Ferimazova N, Reichenberger E. Noonan-like syndrome mutations in PTPN11 in patients diagnosed with cherubism. Clin Genet. 2005;68:190-1 pubmed
- Tartaglia M, Mehler E, Goldberg R, Zampino G, Brunner H, Kremer H, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001;29:465-8 pubmed..1, and genetic heterogeneity has also been documented. Here we show that missense mutations in PTPN11 (MIM 176876)-a gene encoding the nonreceptor protein tyrosine phosphatase SHP-2, which contains two Src homology 2 ..
- Maegawa H, Kashiwagi A, Fujita T, Ugi S, Hasegawa M, Obata T, et al. SHPTP2 serves adapter protein linking between Janus kinase 2 and insulin receptor substrates. Biochem Biophys Res Commun. 1996;228:122-7 pubmed..Thus, SHPTP2 might serve as an adapter protein linking between JAK2 and IRS. These results suggest that JAK1 and JAK2 behave differently and they may constitute a new regulatory component in insulin signaling. ..
- Hoffmann S, Schellack C, Textor S, Konold S, Schmitz D, Cerwenka A, et al. Identification of CLEC12B, an inhibitory receptor on myeloid cells. J Biol Chem. 2007;282:22370-5 pubmed
- Grinnell K, Casserly B, Harrington E. Role of protein tyrosine phosphatase SHP2 in barrier function of pulmonary endothelium. Am J Physiol Lung Cell Mol Physiol. 2010;298:L361-70 pubmed publisher..The SH2 domain-containing nonreceptor PTP, SHP2, is involved in intercellular signaling through direct interaction with adherens junction proteins...
- Lee S, Peng I, Ng Y, Yanagisawa M, Bamji S, Elia L, et al. Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and beta-catenin. J Cell Biol. 2008;183:893-908 pubmed publisher..Our results indicate that a presynaptic signaling pathway through p120ctn, Fer, SHP-2, and beta-catenin promotes excitatory synapse development and function. ..
- Schramm C, Edwards M, Krenz M. New approaches to prevent LEOPARD syndrome-associated cardiac hypertrophy by specifically targeting Shp2-dependent signaling. J Biol Chem. 2013;288:18335-44 pubmed publisherIn LEOPARD syndrome (LS) patients, mutations in the protein tyrosine phosphatase Shp2 cause hypertrophic cardiomyopathy...
- Charest A, Wilker E, McLaughlin M, Lane K, Gowda R, Coven S, et al. ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice. Cancer Res. 2006;66:7473-81 pubmed..These findings provide novel and important insights into the role of ROS and SHP-2 function in solid tumor biology and set the stage for preclinical testing of targeted therapeutic approaches. ..
- Ganesan R, Rasool M. Interleukin 17 regulates SHP-2 and IL-17RA/STAT-3 dependent Cyr61, IL-23 and GM-CSF expression and RANKL mediated osteoclastogenesis by fibroblast-like synoviocytes in rheumatoid arthritis. Mol Immunol. 2017;91:134-144 pubmed publisher..Taken together, our findings demonstrate that IL-17 regulates SHP-2 expression and IL-17RA/STAT-3 dependent production of Cyr61, IL-23, GM-CSF and RANKL in AA-FLS and may reveal a new insight into the pathogenesis of RA. ..
- Yun J, Park S, Jo A, Kang J, Jou I, Park J, et al. Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes. Exp Mol Med. 2011;43:660-8 pubmed publisher..Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress. ..
- Burmeister B, Wang L, Gold M, Skidgel R, O Bryan J, Carnegie G. Protein Kinase A (PKA) Phosphorylation of Shp2 Protein Inhibits Its Phosphatase Activity and Modulates Ligand Specificity. J Biol Chem. 2015;290:12058-67 pubmed publisher..Src homology 2 domain-containing phosphatase (Shp2) is critical for cardiac function because mutations resulting in loss of Shp2 catalytic activity are associated ..
- Arena S, Pattarozzi A, Massa A, Esteve J, Iuliano R, Fusco A, et al. An intracellular multi-effector complex mediates somatostatin receptor 1 activation of phospho-tyrosine phosphatase eta. Mol Endocrinol. 2007;21:229-46 pubmed..In particular the sequential activation of JAK2, SHP-2, and Src conveys the molecular signaling from SSTR1 to the activation of this phosphatase that is responsible for the final biological effects of SST. ..
- Miao H, Burnett E, Kinch M, Simon E, Wang B. Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat Cell Biol. 2000;2:62-9 pubmed..Within one minute after stimulation of EphA2 with its ligand, ephrin-A1, the protein tyrosine phosphatase SHP2 is recruited to EphA2; this is followed by dephosphorylation of FAK and paxillin, and dissociation of the FAK-EphA2 ..
- Mei L, Doherty C, Huganir R. RNA splicing regulates the activity of a SH2 domain-containing protein tyrosine phosphatase. J Biol Chem. 1994;269:12254-62 pubmed
- Pannone L, Bocchinfuso G, Flex E, Rossi C, Baldassarre G, Lissewski C, et al. Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome. Hum Mutat. 2017;38:451-459 pubmed publisherGermline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder...
- Mazharian A, Mori J, Wang Y, Heising S, Neel B, Watson S, et al. Megakaryocyte-specific deletion of the protein-tyrosine phosphatases Shp1 and Shp2 causes abnormal megakaryocyte development, platelet production, and function. Blood. 2013;121:4205-20 pubmed publisherThe SH2 domain-containing protein-tyrosine phosphatases Shp1 and Shp2 have been implicated in regulating signaling from a variety of platelet and megakaryocyte receptors...
- De Rocca Serra Nédélec A, Edouard T, Tréguer K, Tajan M, Araki T, Dance M, et al. Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature. Proc Natl Acad Sci U S A. 2012;109:4257-62 pubmed publisher..syndrome (NS), a genetic disease caused in half of cases by activating mutations of the tyrosine phosphatase SHP2 (PTPN11), is characterized by congenital cardiopathies, facial dysmorphic features, and short stature...
- D Alessio A, Califano D, Incoronato M, Santelli G, Florio T, Schettini G, et al. The tyrosine phosphatase Shp-2 mediates intracellular signaling initiated by Ret mutants. Endocrinology. 2003;144:4298-305 pubmed
- Chen B, Hammonds Odie L, Perron J, Masters B, Bixby J. SHP-2 mediates target-regulated axonal termination and NGF-dependent neurite growth in sympathetic neurons. Dev Biol. 2002;252:170-87 pubmed..The increased sympathetic innervation in target tissues of neurons expressing mutant SHP-2 may result from interference with normal "stop" signals dependent on signaling by gradients of NGF. ..
- Sobreira N, Cirulli E, Avramopoulos D, Wohler E, Oswald G, Stevens E, et al. Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. PLoS Genet. 2010;6:e1000991 pubmed publisher..In the proband, we identified an 11 bp deletion in exon four of PTPN11, which alters frame, results in premature translation termination, and co-segregates with the phenotype...
- Chen B, Bronson R, Klaman L, Hampton T, Wang J, Green P, et al. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet. 2000;24:296-9 pubmed..During studies of genetic interaction between Egfr, encoding the epidermal growth factor receptor, and Ptpn11, encoding the protein-tyrosine-phosphatase Shp2, we discovered that Egfr is required for semilunar, but not ..
- Ohnishi H, Kubota M, Ohtake A, Sato K, Sano S. Activation of protein-tyrosine phosphatase SH-PTP2 by a tyrosine-based activation motif of a novel brain molecule. J Biol Chem. 1996;271:25569-74 pubmed
- Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A. A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature. 1997;386:181-6 pubmed..Our findings indicate that proteins belonging to the SIRP family generally regulate signals defining different physiological and pathological processes. ..
- Schramm C, Fine D, Edwards M, Reeb A, Krenz M. The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling. Am J Physiol Heart Circ Physiol. 2012;302:H231-43 pubmed publisherThe identification of mutations in PTPN11 (encoding the protein tyrosine phosphatase Shp2) in families with congenital heart disease has facilitated mechanistic studies of various cardiovascular defects...
- Fernstrom K, Farmer P, Ali M. Cytoskeletal remodeling in vascular smooth muscle cells in response to angiotensin II-induced activation of the SHP-2 tyrosine phosphatase. J Cell Physiol. 2005;205:402-13 pubmed..These results demonstrate a unique role for SHP-2 in the regulation of the cellular architecture of VSMC, suggesting the possibility that this phosphatase might be instrumental in vascular remodeling. ..
- Salvi M, Stringaro A, Brunati A, Agostinelli E, Arancia G, Clari G, et al. Tyrosine phosphatase activity in mitochondria: presence of Shp-2 phosphatase in mitochondria. Cell Mol Life Sci. 2004;61:2393-404 pubmed..Shp-2 plays a crucial role in a number of intracellular signalling cascades and is probably involved in several human diseases. It thus represents the first tyrosine phosphatase shown to be present in mitochondria. ..
- Puri P, Walker W. The tyrosine phosphatase SHP2 regulates Sertoli cell junction complexes. Biol Reprod. 2013;88:59 pubmed publisher..b>SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) and a key regulator of growth factor-mediated tyrosine kinase ..
- Zhang E, Chapeau E, Hagihara K, Feng G. Neuronal Shp2 tyrosine phosphatase controls energy balance and metabolism. Proc Natl Acad Sci U S A. 2004;101:16064-9 pubmedb>Shp2, a Src homology 2-containing tyrosine phosphatase, has been implicated in a variety of growth factor or cytokine signaling pathways...
- Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012;122:143-59 pubmed publisher..In the present review, we first summarize the IL-6/IL-6R system and IL-6 signal transduction, and then go on to discuss the physiological and pathological roles of IL-6. ..
- Gentile A, Trusolino L, Comoglio P. The Met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev. 2008;27:85-94 pubmed publisher..Several approaches have been recently developed to interfere with the tumorigenic and metastatic processes triggered by Met. ..
- Legius E, Schrander Stumpel C, Schollen E, Pulles Heintzberger C, Gewillig M, Fryns J. PTPN11 mutations in LEOPARD syndrome. J Med Genet. 2002;39:571-4 pubmed..Recently, missense mutations in the PTPN11 gene located in 12q24 were found to cause Noonan syndrome...
- Oak S, Tran C, Castillo M, Thamotharan S, Thamotharan M, Devaskar S. Peroxisome proliferator-activated receptor-gamma agonist improves skeletal muscle insulin signaling in the pregestational intrauterine growth-restricted rat offspring. Am J Physiol Endocrinol Metab. 2009;297:E514-24 pubmed publisher..0002) and SH2-containing protein tyrosine phosphatase 2 (SHP2; P < 0.05) contributing to the rosiglitazone-induced insulin sensitivity was seen only in IUGR+PNGR...
- Huang Y, Cheng C, Chueh S, Hueng D, Huang Y, Chu C, et al. Involvement of SHP2 in focal adhesion, migration and differentiation of neural stem cells. Brain Dev. 2012;34:674-84 pubmed publisherb>SHP2 (Src-homology-2 domain-containing protein tyrosine phosphatase) plays an important role in cell adhesion, migration and cell signaling...
- Mamik M, Ghorpade A. Src homology-2 domain-containing protein tyrosine phosphatase (SHP) 2 and p38 regulate the expression of chemokine CXCL8 in human astrocytes. PLoS ONE. 2012;7:e45596 pubmed publisher..Overexpression of SHP2 and p38 enzymes in astrocytes led to elevated CXCL8 expression; however, inactivating SHP2 and p38 with dominant ..
- Incoronato M, D Alessio A, Paladino S, Zurzolo C, Carlomagno M, Cerchia L, et al. The Shp-1 and Shp-2, tyrosine phosphatases, are recruited on cell membrane in two distinct molecular complexes including Ret oncogenes. Cell Signal. 2004;16:847-56 pubmed..Our results well support the evidence that Ret complexes within and outside rafts mediate distinct biological functions, and indicate that the presence of either Shps participates to determine such functions. ..
- Sarkozy A, Conti E, Digilio M, Marino B, Morini E, Pacileo G, et al. Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. J Med Genet. 2004;41:e68 pubmed
- Barrow A, Astoul E, Floto A, Brooke G, Relou I, Jennings N, et al. Cutting edge: TREM-like transcript-1, a platelet immunoreceptor tyrosine-based inhibition motif encoding costimulatory immunoreceptor that enhances, rather than inhibits, calcium signaling via SHP-2. J Immunol. 2004;172:5838-42 pubmed..Therefore, TLT1 represents a new costimulatory ITIM immunoreceptor and is the second ITIM-bearing receptor to be identified in platelets after platelet endothelial cell adhesion molecule-1. ..
- Khamzina L, Gruppuso P, Wands J. Insulin signaling through insulin receptor substrate 1 and 2 in normal liver development. Gastroenterology. 2003;125:572-85 pubmed..However, insulin-mediated IRS-1/MAPK cascade activation contributes to growth in the adult. ..
- Ali S, Nouhi Z, Chughtai N, Ali S. SHP-2 regulates SOCS-1-mediated Janus kinase-2 ubiquitination/degradation downstream of the prolactin receptor. J Biol Chem. 2003;278:52021-31 pubmed..Together our results provide a novel function for SHP-2 as a positive regulator of cytokine receptor signaling by regulating ubiquitination/degradation pathways. ..
- Yamashita H, Kotani T, Park J, Murata Y, Okazawa H, Ohnishi H, et al. Role of the protein tyrosine phosphatase Shp2 in homeostasis of the intestinal epithelium. PLoS ONE. 2014;9:e92904 pubmed publisher..Src homology 2-containing protein tyrosine phosphatase (Shp2) is a ubiquitously expressed cytoplasmic protein tyrosine phosphatase that functions as a positive regulator of the ..
- Yoo J, Hamburger A. The use of the yeast two hybrid system to evaluate ErbB-3 interactions with SH2 domain containing proteins. Biochem Biophys Res Commun. 1998;251:903-6 pubmed..A double mutant (Asp832Asn, Asp757 His) exhibited a 96 or 350 fold increase in the ability to bind PI3K and Syp. ..