Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PTPN11 (Protein tyrosine phosphatase, non-receptor type, 11)

Identity

Other namesSHP-2
SH-PTP2 (Src homology 2 domain-containing protein tyrosine phosphatase, 2)
PTP2C (Protein tyrosine phosphatase 2C)
BPTP3
HGNC (Hugo) PTPN11
LocusID (NCBI) 5781
Location 12q24.13
Location_base_pair Starts at 112856536 and ends at 112947717 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order centromere - FLJ34154 - RPL6 - PTPN11 - RPH3A - OAS1 - telomere

DNA/RNA

Description The PTPN11 gene is divided in 16 exons. Exon 1 contains the 5' untranslated region and the translation initiation ATG, and a few additional codons. Exon 15 contains the stop codon and exon 16 contains a major portion of the 3' untranslated region. Other features of the PTPN11 gene, such as the promoter region and enhancer elements have not been delineated.
Transcription A 7.0-kb transcript is detected in several tissues (heart, brain, lung, liver, skeletal muscle, kidney, and pancreas) with highest steady-state levels in heart and skeletal muscle. The predominant human PTPN11 mRNA contains an open reading frame of 1,779 bases, resulting in a predicted protein of 593 amino acid residues. A second mRNA containing 12 additional base pairs (exon 11) has been identified. Little additional information is available about this alternative transcript.
Pseudogene A number of PTPN11-related processed pseudogenes, i.e. with no apparent exon structure, have been documented in the human genome. All the pseudogenes share >92% nucleotide identity with the PTPN11 cDNA (including the 5'-UTR and 3'-UTR), but harbour frameshift mutations and multiple stop codons. Three of the five pseudogenes appear to be expressed with distinct tissue distributions and expression levels.

Protein

 
  PTPN11 genomic organization and SHP-2 domain structure:
Figure 1 : (A) The PTPN11 gene and SHP-2 domain characterization. The coding exons are shown as numbered filled boxes. The functional domains of the protein, comprising two tandemly arranged SH2 domains at the N terminus (N-SH2 and C-SH2) followed by a protein tyrosine phosphatase (PTP) domain, are shown below. Numbers below the domain structure indicate the amino-acid boundaries of those domains. (B) Three-dimensional structure of SHP-2 in its catalytically inactive conformation, as determined by Hof et al. (1998). Residues involved in catalysis are shown (space fill).
Figure 2 : Location of SHP-2 mutated residues in human disease. (A) Noonan syndrome and LEOPARD syndrome (germ-line origin; N=224); (B) Noonan syndrome with juvenile myelomonocytic leukemia (germ-line origin; N=11); (C) hematologic malignancies, including juvenile myelomonocytic leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia (somatic origin; N=97). The pictures show the C trace of SHP-2 in its catalytically inactive conformation. Affected residues are indicated with their side chains as black sticks.
Description SHP-2 is a member of a small subfamily of cytoplasmic Src homology 2 (SH2) domain-containing protein tyrosine phosphatases. Both the N-SH2 and C-SH2 domains selectively bind to short amino acid motifs containing a phosphotyrosyl residue and promote SHP-2 association with activated receptors and other signaling partners. Crystallographic data indicate that the N-SH2 domain also interacts with the PTP domain using a separate site. As these subdomains show negative cooperativity, the N-SH2 domain functions as an intramolecular switch controlling SHP-2 catalytic activation. Specifically, the N-SH2 domain interacts with the PTP domain basally, blocking the catalytic site. Binding of the N-SH2 phosphopeptide-binding site to the phosphotyrosyl ligand promotes a conformational change of the domain that weakens the auto-inhibiting intramolecular interaction, making the catalytic site available to substrate, thereby activating the phosphatase.
Expression Widely expressed in both embryonic and adult tissues.
Localisation Cytoplasmic. It binds to activated cell surface receptors, cell adhesion molecules and scaffolding adapters.
Function SHP-2 functions as an intracellular signal transducer. It positively modulates signal flow in most circumstances, but can also function as negative regulator depending upon its binding partner and interactions with downstream signaling networks. SHP-2 positively controls the activation of the RAS/MAPK cascade induced by several growth factors, and negatively regulates JAK/STAT signaling. In most cases, SHP-2's function in intracellular signaling appears to be immediately proximal to activated receptors and upstream to RAS. The mechanisms of SHP-2's action and its physiological substrates are still poorly defined. However, both membrane translocation and PTPase activity are required for SHP-2 function. SHP-2 is required during development. Embryos nullizygous for Shp-2 have defects in gastrulation and mesodermal patterning resulting in severe abnormalities in axial and paraxial mesodermal structures. Shp-2 function is also required for development of terminal and skeletal structures, semilunar valvulogenesis in the heart, and hematopoiesis.
Homology PTPN6 (protein tyrosine phosphatase, non-receptor type, 6) previously known as SHP1 or SHP-1 (Src homology 2 domain-containing protein tyrosine phosphatase, 1).

Mutations

Note At least two distinct classes of PTPN11 mutations have been identified in humans.
  • The first group, which has germ-line origin, causes Noonan syndrome and closely related developmental disorders.
  • The second group, acquired as a somatic event, has been documented in a heterogeneous group of hematologic malignancies and pre-leukemic disorders, and rarely in certain solid tumors.
    The vast majority of mutations affect residues residing at or close to the interface between the N-SH2 and PTP domains. Increasing evidence supports that both germ-line and somatic mutations promote SHP-2 gain-of-function by destabilizing the catalytically inactive conformation of the protein, and prolong signal flux through the RAS/MAPK pathway in a ligand-dependent manner.
    A mouse model bearing the NS-causative D61G mutation in the Ptpn11 gene has been recently generated and characterized. The Ptpn11D61G/D61G genotype is embryonic lethal. At day E13.5, these embryos are grossly edematous and hemorrhagic, have diffuse liver necrosis and severe cardiac defects. Heterozygous embryos exhibit cardiac defects, proportionate growth failure and perturbed craniofacial development. Hematologic anomalies include a mild myeloproliferative disease. Ptpn11D61G/+ embryonic fibroblasts exhibit a three-fold increased Shp-2 activity and increased association of Shp-2 with Gab1 after stimulation with EGF. Cell culture and whole embryo studies reveal that increased RAS/MAPK signaling is variably present, appearing to be cell-context specific.
  • Germinal Selection: 124A>G (T42A), 179-181delGTG (delGly60), 181-183delGAT (delAsp61), 182A>G (D61G), 184T>G (Y62D), 188A>G (Y63C), 214G>T (A72S), 215C>G (A72G), 218C>T (T73I), 228G>T,C (E76D), 236A>G (N79R), 317A>C (D106A), 836A>G (Y279C), 922A>G (N308D), 1403C>T (T468M), 1510A>G (M504V).
    Somatic Selection: 181G>T (D61Y), 182A>T (D61V), 205G>A (E69K), 211-213TTT>AAA (F71K), 214G>A (A72T), 215C>T (A72V), 226G>A (E76K), 226G>C (E76Q), 227A>T (E76V), 227A>G (E76G), 227A>C (E76A), 1471C>T (P491S), 1472C>T (P491L), 1504T>C (S502P), 1504T>G (S502A), 1520C>A (T507K), 1528C>A (Q510K).

    Implicated in

    Entity Noonan syndrome, Noonan-like/multiple giant cell lesion syndrome and LEOPARD syndrome.
    Note Germ-line origin. Gain-of-function mutations. Increased basal protein tyrosine phosphatase activity. Prolonged ligand-dependent activation of the RAS/MAPK cascade.
    Disease Noonan syndrome is a genetically heterogeneous and clinically variable developmental disorder defined by short stature, facial dysmorphism and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, down-slanting palpebral fissures, ptosis, high-arched palate and low-set, posteriorly rotated ears. Cardiovascular abnormalities, primarily pulmonic stenosis and hypertrophic cardiomyopathy, are present in up to 85% of affected individuals. Additional relatively frequent features are multiple skeletal defects, webbed neck, mental retardation, cryptorchidism and bleeding diathesis. Children with Noonan syndrome are predisposed to a spectrum of hematologic abnormalities, including transient monocytosis, thrombocytopenia and rarely juvenile myelomonocytic leukemia and acute leukemia.
      
    Entity Juvenile myelomonocytic leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, melanoma, neuroblastoma, lung adenocarcinoma, colon cancer.
    Note Somatic origin.
    Prognosis No data are currently available.
    Oncogenesis Gain-of-function mutations. Increased basal protein tyrosine phosphatase activity. Prolonged ligand-dependent activation of the RAS/MAPK cascade.
      

    External links

    Nomenclature
    HGNC (Hugo)PTPN11   9644
    Cards
    AtlasPTPN11ID41910ch12q24
    Entrez_Gene (NCBI)PTPN11  5781  protein tyrosine phosphatase, non-receptor type 11
    GeneCards (Weizmann)PTPN11
    Ensembl (Hinxton)ENSG00000179295 [Gene_View]  chr12:112856536-112947717 [Contig_View]  PTPN11 [Vega]
    ICGC DataPortalENSG00000179295
    AceView (NCBI)PTPN11
    Genatlas (Paris)PTPN11
    WikiGenes5781
    SOURCE (Princeton)NM_002834 NM_080601
    Genomic and cartography
    GoldenPath (UCSC)PTPN11  -  12q24.13   chr12:112856536-112947717 +  12q24.1   [Description]    (hg19-Feb_2009)
    EnsemblPTPN11 - 12q24.1 [CytoView]
    Mapping of homologs : NCBIPTPN11 [Mapview]
    OMIM151100   156250   163950   176876   607785   
    Gene and transcription
    Genbank (Entrez)AK289854 AK312147 AU123593 BC007869 BC008692
    RefSeq transcript (Entrez)NM_002834 NM_080601
    RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_007459 NT_029419 NW_001838063 NW_004929385
    Consensus coding sequences : CCDS (NCBI)PTPN11
    Cluster EST : UnigeneHs.506852 [ NCBI ]
    CGAP (NCI)Hs.506852
    Alternative Splicing : Fast-db (Paris)GSHG0007014
    Alternative Splicing GalleryENSG00000179295
    Gene ExpressionPTPN11 [ NCBI-GEO ]     PTPN11 [ SEEK ]   PTPN11 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ06124 (Uniprot)
    NextProtQ06124  [Medical]
    With graphics : InterProQ06124
    Splice isoforms : SwissVarQ06124 (Swissvar)
    Catalytic activity : Enzyme3.1.3.48 [ Enzyme-Expasy ]   3.1.3.483.1.3.48 [ IntEnz-EBI ]   3.1.3.48 [ BRENDA ]   3.1.3.48 [ KEGG ]   
    Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    TYR_PHOSPHATASE_1 (PS00383)    TYR_PHOSPHATASE_2 (PS50056)    TYR_PHOSPHATASE_PTP (PS50055)   
    Domains : Interpro (EBI)Prot-tyrosine_phosphatase-like    SH2    Tyr/Dual-sp_Pase    Tyr_Pase_AS    Tyr_Pase_non-rcpt_typ-6/11    Tyr_Pase_rcpt/non-rcpt   
    Related proteins : CluSTrQ06124
    Domain families : Pfam (Sanger)SH2 (PF00017)    Y_phosphatase (PF00102)   
    Domain families : Pfam (NCBI)pfam00017    pfam00102   
    Domain families : Smart (EMBL)PTPc (SM00194)  SH2 (SM00252)  
    DMDM Disease mutations5781
    Blocks (Seattle)Q06124
    PDB (SRS)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG   
    PDB (PDBSum)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG   
    PDB (IMB)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG   
    PDB (RSDB)2SHP    3B7O    3MOW    3O5X    3TKZ    3TL0    3ZM0    3ZM1    3ZM2    3ZM3    4DGP    4DGX    4GWF    4H1O    4H34    4JE4    4JEG    4JMG   
    Human Protein AtlasENSG00000179295
    Peptide AtlasQ06124
    HPRD01470
    IPIIPI00658023   IPI00298347   IPI00658002   IPI00063246   IPI00981283   
    Protein Interaction databases
    DIP (DOE-UCLA)Q06124
    IntAct (EBI)Q06124
    FunCoupENSG00000179295
    BioGRIDPTPN11
    IntegromeDBPTPN11
    STRING (EMBL)PTPN11
    Ontologies - Pathways
    QuickGOQ06124
    Ontology : AmiGODNA damage checkpoint  activation of MAPK activity  phosphoprotein phosphatase activity  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  SH3/SH2 adaptor activity  insulin receptor binding  protein binding  nucleus  cytoplasm  mitochondrion  cytosol  triglyceride metabolic process  epidermal growth factor receptor signaling pathway  axon guidance  brain development  heart development  blood coagulation  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  hormone-mediated signaling pathway  cytokine-mediated signaling pathway  protein domain specific binding  receptor tyrosine kinase binding  T cell costimulation  D1 dopamine receptor binding  regulation of cell adhesion mediated by integrin  organ growth  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  atrioventricular canal development  Fc-epsilon receptor signaling pathway  ERBB signaling pathway  regulation of multicellular organism growth  hormone metabolic process  glucose homeostasis  protein complex  phospholipase binding  insulin receptor substrate binding  innate immune response  negative regulation of insulin secretion  regulation of protein export from nucleus  positive regulation of hormone secretion  neurotrophin TRK receptor signaling pathway  ephrin receptor signaling pathway  phosphatidylinositol-mediated signaling  multicellular organismal reproductive process  genitalia development  inner ear development  leukocyte migration  peptide hormone receptor binding  negative regulation of cortisol secretion  negative regulation of growth hormone secretion  face morphogenesis  interferon-gamma-mediated signaling pathway  regulation of interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  regulation of type I interferon-mediated signaling pathway  positive regulation of glucose import in response to insulin stimulus  
    Ontology : EGO-EBIDNA damage checkpoint  activation of MAPK activity  phosphoprotein phosphatase activity  protein tyrosine phosphatase activity  protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  non-membrane spanning protein tyrosine phosphatase activity  SH3/SH2 adaptor activity  insulin receptor binding  protein binding  nucleus  cytoplasm  mitochondrion  cytosol  triglyceride metabolic process  epidermal growth factor receptor signaling pathway  axon guidance  brain development  heart development  blood coagulation  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  hormone-mediated signaling pathway  cytokine-mediated signaling pathway  protein domain specific binding  receptor tyrosine kinase binding  T cell costimulation  D1 dopamine receptor binding  regulation of cell adhesion mediated by integrin  organ growth  peptidyl-tyrosine dephosphorylation  peptidyl-tyrosine dephosphorylation  atrioventricular canal development  Fc-epsilon receptor signaling pathway  ERBB signaling pathway  regulation of multicellular organism growth  hormone metabolic process  glucose homeostasis  protein complex  phospholipase binding  insulin receptor substrate binding  innate immune response  negative regulation of insulin secretion  regulation of protein export from nucleus  positive regulation of hormone secretion  neurotrophin TRK receptor signaling pathway  ephrin receptor signaling pathway  phosphatidylinositol-mediated signaling  multicellular organismal reproductive process  genitalia development  inner ear development  leukocyte migration  peptide hormone receptor binding  negative regulation of cortisol secretion  negative regulation of growth hormone secretion  face morphogenesis  interferon-gamma-mediated signaling pathway  regulation of interferon-gamma-mediated signaling pathway  type I interferon signaling pathway  regulation of type I interferon-mediated signaling pathway  positive regulation of glucose import in response to insulin stimulus  
    Pathways : BIOCARTASignaling of Hepatocyte Growth Factor Receptor [Genes]    Insulin Signaling Pathway [Genes]    The Co-Stimulatory Signal During T-cell Activation [Genes]    IGF-1 Signaling Pathway [Genes]    IL 6 signaling pathway [Genes]   
    Pathways : KEGGRas signaling pathway    Jak-STAT signaling pathway    Natural killer cell mediated cytotoxicity    Leukocyte transendothelial migration    Neurotrophin signaling pathway    Adipocytokine signaling pathway    Epithelial cell signaling in Helicobacter pylori infection    Herpes simplex infection    Proteoglycans in cancer    Renal cell carcinoma    Chronic myeloid leukemia   
    REACTOMEQ06124 [protein]
    REACTOME PathwaysREACT_111155 Cell-Cell communication [pathway]
    REACTOME PathwaysREACT_111045 Developmental Biology [pathway]
    REACTOME PathwaysREACT_116125 Disease [pathway]
    REACTOME PathwaysREACT_604 Hemostasis [pathway]
    REACTOME PathwaysREACT_6900 Immune System [pathway]
    REACTOME PathwaysREACT_111102 Signal Transduction [pathway]
    Protein Interaction DatabasePTPN11
    Wikipedia pathwaysPTPN11
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)PTPN11
    SNP (GeneSNP Utah)PTPN11
    SNP : HGBasePTPN11
    Genetic variants : HAPMAPPTPN11
    1000_GenomesPTPN11 
    ICGC programENSG00000179295 
    Cancer Gene: CensusPTPN11 
    CONAN: Copy Number AnalysisPTPN11 
    Somatic Mutations in Cancer : COSMICPTPN11 
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    DECIPHER (Syndromes)12:112856536-112947717
    Mutations and Diseases : HGMDPTPN11
    OMIM151100    156250    163950    176876    607785   
    MedgenPTPN11
    GENETestsPTPN11
    Disease Genetic AssociationPTPN11
    Huge Navigator PTPN11 [HugePedia]  PTPN11 [HugeCancerGEM]
    Genomic VariantsPTPN11  PTPN11 [DGVbeta]
    Exome VariantPTPN11
    dbVarPTPN11
    ClinVarPTPN11
    snp3D : Map Gene to Disease5781
    General knowledge
    Homologs : HomoloGenePTPN11
    Homology/Alignments : Family Browser (UCSC)PTPN11
    Phylogenetic Trees/Animal Genes : TreeFamPTPN11
    Chemical/Protein Interactions : CTD5781
    Chemical/Pharm GKB GenePA33986
    Clinical trialPTPN11
    Cancer Resource (Charite)ENSG00000179295
    Other databases
    Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=PTPN11
    Probes
    Litterature
    PubMed499 Pubmed reference(s) in Entrez
    CoreMinePTPN11
    GoPubMedPTPN11
    iHOPPTPN11

    Bibliography

    A widely expressed human protein-tyrosine phosphatase containing src homology 2 domains.
    Ahmad S, Banville D, Zhao Z, Fischer EH, Shen SH
    Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (6) : 2197-2201.
    PMID 7681589
     
    Crystal structure of the tyrosine phosphatase SHP-2.
    Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE
    Cell. 1998 ; 92 (4) : 441-450.
    PMID 9491886
     
    Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.
    Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD
    Nature genetics. 2001 ; 29 (4) : 465-468.
    PMID 11704759
     
    Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene.
    Digilio MC, Conti E, Sarkozy A, Mingarelli R, Dottorini T, Marino B, Pizzuti A, Dallapiccola B
    American journal of human genetics. 2002 ; 71 (2) : 389-394.
    PMID 12058348
     
    PTPN11 mutations in LEOPARD syndrome.
    Legius E, Schrander-Stumpel C, Schollen E, Pulles-Heintzberger C, Gewillig M, Fryns JP
    Journal of medical genetics. 2002 ; 39 (8) : 571-574.
    PMID 12161596
     
    PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.
    Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD
    American journal of human genetics. 2002 ; 70 (6) : 1555-1563.
    PMID 11992261
     
    The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling.
    Neel BG, Gu H, Pao L
    Trends in biochemical sciences. 2003 ; 28 (6) : 284-293.
    PMID 12826400
     
    Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia.
    Tartaglia M, Niemeyer CM, Fragale A, Song X, Buechner J, Jung A, Hˆ§hlen K, Hasle H, Licht JD, Gelb BD
    Nature genetics. 2003 ; 34 (2) : 148-150.
    PMID 12717436
     
    A genomic perspective on protein tyrosine phosphatases: gene structure, pseudogenes, and genetic disease linkage.
    Andersen JN, Jansen PG, Echwald SM, Mortensen OH, Fukada T, Del Vecchio R, Tonks NK, Mˆ½ller NP
    The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2004 ; 18 (1) : 8-30.
    PMID 14718383
     
    Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation.
    Araki T, Mohi MG, Ismat FA, Bronson RT, Williams IR, Kutok JL, Yang W, Pao LI, Gilliland DG, Epstein JA, Neel BG
    Nature medicine. 2004 ; 10 (8) : 849-857.
    PMID 15273746
     
    Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia.
    Bentires-Alj M, Paez JG, David FS, Keilhack H, Halmos B, Naoki K, Maris JM, Richardson A, Bardelli A, Sugarbaker DJ, Richards WG, Du J, Girard L, Minna JD, Loh ML, Fisher DE, Velculescu VE, Vogelstein B, Meyerson M, Sellers WR, Neel BG
    Cancer research. 2004 ; 64 (24) : 8816-8820.
    PMID 15604238
     
    Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1 binding and sustained ERK2/MAPK1 activation.
    Fragale A, Tartaglia M, Wu J, Gelb BD
    Human mutation. 2004 ; 23 (3) : 267-277.
    PMID 14974085
     
    PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group.
    Loh ML, Reynolds MG, Vattikuti S, Gerbing RB, Alonzo TA, Carlson E, Cheng JW, Lee CM, Lange BJ, Children's Cancer Group, Meshinchi S
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 ; 18 (11) : 1831-1834.
    PMID 15385933
     
    Mutations in PTPN11 implicate the SHP-2 phosphatase in leukemogenesis.
    Loh ML, Vattikuti S, Schubbert S, Reynolds MG, Carlson E, Lieuw KH, Cheng JW, Lee CM, Stokoe D, Bonifas JM, Curtiss NP, Gotlib J, Meshinchi S, Le Beau MM, Emanuel PD, Shannon KM
    Blood. 2004 ; 103 (6) : 2325-2331.
    PMID 14644997
     
    Paternal germline origin and sex-ratio distortion in transmission of PTPN11 mutations in Noonan syndrome.
    Tartaglia M, Cordeddu V, Chang H, Shaw A, Kalidas K, Crosby A, Patton MA, Sorcini M, van der Burgt I, Jeffery S, Gelb BD
    American journal of human genetics. 2004 ; 75 (3) : 492-497.
    PMID 15248152
     
    Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia.
    Tartaglia M, Martinelli S, Cazzaniga G, Cordeddu V, Iavarone I, Spinelli M, Palmi C, Carta C, Pession A, Aricˆ¾ M, Masera G, Basso G, Sorcini M, Gelb BD, Biondi A
    Blood. 2004 ; 104 (2) : 307-313.
    PMID 14982869
     
    SHP-2 and myeloid malignancies.
    Tartaglia M, Niemeyer CM, Shannon KM, Loh ML
    Current opinion in hematology. 2004 ; 11 (1) : 44-50.
    PMID 14676626
     
    Genotype-phenotype correlations in Noonan syndrome.
    Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A
    The Journal of pediatrics. 2004 ; 144 (3) : 368-374.
    PMID 15001945
     
    Germ-line and somatic PTPN11 mutations in human disease.
    Tartaglia M, Gelb BD
    European journal of medical genetics. 2005 ; 48 (2) : 81-96.
    PMID 16053901
     
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    Contributor(s)

    Written02-2005Marco Tartaglia, Bruce D Gelb

    Citation

    This paper should be referenced as such :
    Tartaglia, M ; Gelb, BD
    PTPN11 (protein tyrosine phosphatase, non-receptor type, 11)
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(2):123-126.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/PTPN11ID41910ch12q24.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sat Nov 8 16:47:42 CET 2014

    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.