Atlas of Genetics and Cytogenetics in Oncology and Haematology


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GRB2 (Growth factor receptor-bound protein 2)

Identity

Other namesASH (Abundant Src Homology)
Grb3-3
MST084
MSTP084
HTO27
EGFRBP (Epidermal Growth Factor Receptor Binding Protein)-GRB2
HGNC (Hugo) GRB2
LocusID (NCBI) 2885
Location 17q25.1
Location_base_pair Starts at 73314157 and ends at 73401789 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Chromosome 17, 87,632 bases, 5'- 70913384 - 70825752 -3'; strand: (-). The human GRB2 gene is telomeric to GGA3 (Golgi associated, gamma adaptin ear containing, ARF binding protein 3) and centromeric to ITGB4 (integrin, beta 4).

DNA/RNA

Transcription The GRB2 gene structure consists of five exons (ranging from 78 to 186 bp) and four introns (from approximately 1 to approximately 7 kb). Two human mRNA transcript variants arise from alternative splicing. GRB2 variant 1 mRNA encodes protein isoform 1, which is longer. Variant 2 mRNA, which encodes protein isoform 2, lacks an in-frame exon present in the 3' coding region of variant 1 encompassing residues 59 - 100 of the mature protein (see Protein, below).
Pseudogene At least one potential human pseudogene may exist: LOC391157. A pseudogene of the mouse Grb2 homolog, known as Grb2-ps1 (growth factor receptor bound protein 2, pseudogene 1) also has been identified.

Protein

 
  A schematic representation of the domain structure of GRB2, which consists of a single Src homology 2 (SH2) domain (residues 59 - 152) flanked by two SH3 domains (amino-terminal: residues 3 - 54; carboxy-terminal: residues 160-212).
Description GRB2 (isoform 1) is a 217 residue protein with an expected molecular mass of 25,206 Da. GRB2 protein has homology to non-catalytic regions of c-Src, consisting of a single Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. GRB2 isoform 2, encoded by an alternatively spliced mRNA transcript known as variant 2, has a deletion in the amino-terminal portion of the SH2 domain encompassing residues 59 - 100 of isoform 1. This protein isoform, known originally as GRB3-3, does not bind to phosphotyrosyl-containing proteins like isoform 1, but retains two functional SH3 domains.
Expression Expressed in virtually all embryonic and adult tissues.
Localisation Primarily cytosolic, but transient plasma membrane and nuclear localizations have been reported.
Function Cell surface receptor signaling - The two GRB2 SH3 domains bind to the proline-rich regions of the guanine nucleotide releasing factor son of sevenless (SOS-1) protein, and the GRB2-SOS-1 complex preexists in the cytoplasm of resting cells. Phosphotyrosyl residues on in the context of the motif NH2- pYXNX-COOH (where pY represents phosphotyrosine, N represents asparagine, and X represents any other residue) are selectively recognized by the GRB2 SH2 domain. Growth factor receptor tyrosine kinases (RTKs), including those for epidermal growth factor (EGF), fibroblast growth factor, nerve growth factor (TrkA/TrkB), platelet-derived growth factor, colony-stimulating factor-1, and hepatocyte growth factor (HGF), as well as non-receptor tyrosine kinases (TKs) such as BCR-Abl and focal adhesion kinase (FAK), intracellular effectors such as insulin receptor substrate-1 and Shc, and phosphotyrosine phosphatases such as SHP-2 (PTPN11) and receptor-like tyrosine phosphatase alpha, all conditionally possess the pYXNX motif. Note that the environmental cue leading to protein tyrosyl phosphorylation on an appropriate GRB2 recognition motif is independent of GRB2 interaction; thus, ligand independent EGFR activation, such as growth hormone-induced EGFR tyrosine phosphorylation by JAK2, also leads to GRB2-mediated ERK kinase pathway activation and c-fos expression. Similarly, mechanical stress leading to increased angiotensin II production and transactivation of EGFR and other intracellular kinases implicates GRB2 recruitment in cardiac hypertrophy and myocardial remodeling.
In many mitogenic signaling pathways, recruitment of GRB2 from the cytosol, where it is already bound to the guanine nucleotide exchange factor SOS-1 via its amino-terminal SH3 domain, brings SOS1 in close proximity to Ras at the plasma membrane. Ras, a small GTPase in the GDP-bound inactive state in quiescent cells, then undergoes nucleotide exchange of GDP for GTP, which facilitates binding of the serine/threonine protein kinase Raf-1 and its subsequent activation. This initiates a cascade of kinase activation: activated Raf-1 phosphorylates and activates MEK1/MEK2, which in turn phosphorylate and stimulate the MAP kinases ERK1/ERK2. Activated ERKs translocate to the nucleus and phosphorylate transcription factors such as Elk-1, STAT1, STAT3 and Myc, activating gene expression. In parallel, the phosphatidyl inositol 3-kinase (PI3K)/Akt pathway is activated via the adaptor Gab1, which is bound to the GRB2 carboxyl-terminal SH3 domain in many epithelial cell types. The gene expression programs activated by these pathways initiate a spectrum of fundamental cellular activities including proliferation, growth (increase in cell size), differentiation and survival. These processes are critical for normal embryonic development and adult homeostasis, and are frequently aberrantly activated in cancer.
Stimulation of the T cell antigen receptor (TCR) induces the tyrosine phosphorylation of a variety of cellular proteins, including a protein called p36-38 or Linker for Activation of T cells (LAT), a protein tightly associated with the plasma membrane. Tyrosyl-phosphorylated sequences of LAT bind to the GRB2 SH2 domain. In these cells the SH3 domains of GRB2 bind Vav-family proteins, guanine nucleotide exchange factors for Rho-family GTPases. These interactions are essential for TCR-induced calcium flux and activation of the MAP kinase cascade, ultimately leading to T cell proliferation and effector functions.
Receptor endocytosis and ubiquitinylation - Upon ligand-dependant activation of EGFR TK, c-Cbl binds to the EGFR directly through its SH2 domain and indirectly through its SH3 domain. c-Cbl binding and its consequential phosphorylation results in activation of the E3 ubiquitin ligase complex of which c-Cbl is a component, resulting in receptor ubiquitinylation. GRB2 also regulates internalization of EGF receptors through clathrin-coated pits.
Actin-based cell motility - GRB2 participates directly in the regulation of actin filament formation and actin-based cell motility. GRB2 is a critical link between Wiskott-Aldrich Syndrome protein (WASp) and the actin cytoskeleton; WAS patients show defects in T cell polarization and migration in response to physiologic stimuli, resulting in thrombocytopenia, eczema and immunodeficiency. Studies of WASp function and the intracellular motility of invasive microbial pathogens such as Listeria monocytogenes and Vaccinia virus helped to elucidate an important role for GRB2 in directly promoting actin based motility. In most mammalian cells, the WASp family member N-WASp interacts with the Arp2/3 complex and G-actin to stimulate actin polymerization. N-WASp activity is enhanced by other effectors such as Nck, Cdc42 and GRB2; disruption of GRB2 SH3 or SH2 domains diminishes actin polymerization and thus actin-based motility.
Homology GRB2 amino acid sequence is very highly conserved among species. Human GRB2 shows 50% overall amino acid sequence identity with S. cerevisiae YPR154w, 58% identity with Sem-5 of C. elegans, 66% identity with the D. melanogaster homolog Drk and over 99% identity with both rat and mouse homologs.

Mutations

Note No known naturally-occurring mutations in human GRB2 have been reported.

Implicated in

Entity Normal embryogenesis
Note A null mutation introduced into the mouse gene for Grb2 was used to demonstrate that Grb2 is required during embryogenesis for the differentiation of endodermal cells and epiblast formation. Replacing the carboxy-terminus of SOS-1 with the Grb2 SH2 domain yielded a fusion protein that rescued the defects caused by this Grb2 mutation. Grb2 signaling primarily regulates differentiation, rather than proliferation, in the early mouse embryo.
  
Entity Cardiac hypertrophy
Note Engineered Grb2 +/- mice subjected to cardiac stress failed to activate p38 MAP kinase (MAPK14) and Jun N-terminal kinase (JNK), and the cardiac hypertrophy and fibrosis observed in normal mice were blocked. Transgenic mice with dominant-negative forms of MAPK p38-alpha and p38-beta developed cardiac hypertrophy but were resistant to cardiac fibrosis when subjected to cardiac stress. These and other findings suggest that Grb2 activity is essential for cardiac hypertrophy and fibrosis in response to pressure overload, and that different signaling pathways downstream of Grb2 regulate fibrosis, fetal gene induction, and cardiomyocyte growth.
  
Entity Cancer
Note As a pivotal activator of cell-cycle control and motility pathways downstream of several growth factor receptors, GRB2 is involved in oncogenic signaling in a wide variety of human tumors. For example, GRB2 directly interacts with SOS-1 and the Bcr portion of the Bcr-Abl fusion protein, a tyrosine kinase oncoprotein which has been implicated in the pathogenesis of Philadelphia chromosome positive leukemias, such as CML, ALL, and AML. GRB2 is rate limiting for mammary carcinomas induced by polyomavirus middle T antigen. GRB2 over expression has been reported in human breast, bladder and prostate cancer cell lines. Selective small molecule inhibitors of GRB2 SH2 domain binding block solid tumor metastasis in animal models.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias t0817q24q22ID1494

External links

Nomenclature
HGNC (Hugo)GRB2   4566
Cards
AtlasGRB2ID386ch17q25
Entrez_Gene (NCBI)GRB2  2885  growth factor receptor-bound protein 2
GeneCards (Weizmann)GRB2
Ensembl (Hinxton)ENSG00000177885 [Gene_View]  chr17:73314157-73401789 [Contig_View]  GRB2 [Vega]
ICGC DataPortalENSG00000177885
cBioPortalGRB2
AceView (NCBI)GRB2
Genatlas (Paris)GRB2
WikiGenes2885
SOURCE (Princeton)NM_002086 NM_203506
Genomic and cartography
GoldenPath (UCSC)GRB2  -  17q25.1   chr17:73314157-73401789 -  17q24-q25   [Description]    (hg19-Feb_2009)
EnsemblGRB2 - 17q24-q25 [CytoView]
Mapping of homologs : NCBIGRB2 [Mapview]
OMIM108355   
Gene and transcription
Genbank (Entrez)AA452034 AF171699 AF246238 AF302079 AF498925
RefSeq transcript (Entrez)NM_002086 NM_203506
RefSeq genomic (Entrez)AC_000149 NC_000017 NC_018928 NG_029556 NT_010783 NW_001838454 NW_004929407
Consensus coding sequences : CCDS (NCBI)GRB2
Cluster EST : UnigeneHs.444356 [ NCBI ]
CGAP (NCI)Hs.444356
Alternative Splicing : Fast-db (Paris)GSHG0013729
Alternative Splicing GalleryENSG00000177885
Gene ExpressionGRB2 [ NCBI-GEO ]     GRB2 [ SEEK ]   GRB2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP62993 (Uniprot)
NextProtP62993  [Medical]
With graphics : InterProP62993
Splice isoforms : SwissVarP62993 (Swissvar)
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)    SH3 (PS50002)   
Domains : Interpro (EBI)SH2 [organisation]   SH3_domain [organisation]  
Related proteins : CluSTrP62993
Domain families : Pfam (Sanger)SH2 (PF00017)    SH3_1 (PF00018)   
Domain families : Pfam (NCBI)pfam00017    pfam00018   
Domain families : Smart (EMBL)SH2 (SM00252)  SH3 (SM00326)  
DMDM Disease mutations2885
Blocks (Seattle)P62993
PDB (SRS)1AZE    1BM2    1BMB    1CJ1    1FHS    1FYR    1GCQ    1GFC    1GFD    1GHU    1GRI    1IO6    1JYQ    1JYR    1JYU    1QG1    1TZE    1X0N    1ZFP    2AOA    2AOB    2H46    2H5K    2HUW    2VVK    2VWF    2W0Z    3C7I    3IMD    3IMJ    3IN7    3IN8    3KFJ    3MXC    3MXY    3N7Y    3N84    3N8M    3OV1    3OVE    3S8L    3S8N    3S8O    3WA4   
PDB (PDBSum)1AZE    1BM2    1BMB    1CJ1    1FHS    1FYR    1GCQ    1GFC    1GFD    1GHU    1GRI    1IO6    1JYQ    1JYR    1JYU    1QG1    1TZE    1X0N    1ZFP    2AOA    2AOB    2H46    2H5K    2HUW    2VVK    2VWF    2W0Z    3C7I    3IMD    3IMJ    3IN7    3IN8    3KFJ    3MXC    3MXY    3N7Y    3N84    3N8M    3OV1    3OVE    3S8L    3S8N    3S8O    3WA4   
PDB (IMB)1AZE    1BM2    1BMB    1CJ1    1FHS    1FYR    1GCQ    1GFC    1GFD    1GHU    1GRI    1IO6    1JYQ    1JYR    1JYU    1QG1    1TZE    1X0N    1ZFP    2AOA    2AOB    2H46    2H5K    2HUW    2VVK    2VWF    2W0Z    3C7I    3IMD    3IMJ    3IN7    3IN8    3KFJ    3MXC    3MXY    3N7Y    3N84    3N8M    3OV1    3OVE    3S8L    3S8N    3S8O    3WA4   
PDB (RSDB)1AZE    1BM2    1BMB    1CJ1    1FHS    1FYR    1GCQ    1GFC    1GFD    1GHU    1GRI    1IO6    1JYQ    1JYR    1JYU    1QG1    1TZE    1X0N    1ZFP    2AOA    2AOB    2H46    2H5K    2HUW    2VVK    2VWF    2W0Z    3C7I    3IMD    3IMJ    3IN7    3IN8    3KFJ    3MXC    3MXY    3N7Y    3N84    3N8M    3OV1    3OVE    3S8L    3S8N    3S8O    3WA4   
Human Protein AtlasENSG00000177885 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP62993
HPRD00150
IPIIPI00021327   IPI00218070   
Protein Interaction databases
DIP (DOE-UCLA)P62993
IntAct (EBI)P62993
FunCoupENSG00000177885
BioGRIDGRB2
InParanoidP62993
Interologous Interaction database P62993
IntegromeDBGRB2
STRING (EMBL)GRB2
Ontologies - Pathways
Ontology : AmiGOphosphotyrosine binding  SH3/SH2 adaptor activity  epidermal growth factor receptor binding  neurotrophin TRKA receptor binding  protein binding  nucleus  cytoplasm  endosome  Golgi apparatus  cytosol  plasma membrane  epidermal growth factor receptor signaling pathway  Ras protein signal transduction  cell-cell signaling  axon guidance  aging  blood coagulation  COP9 signalosome  insulin receptor signaling pathway  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  positive regulation of signal transduction  positive regulation of signal transduction  vesicle membrane  viral process  SH3 domain binding  protein kinase binding  protein phosphatase binding  platelet activation  positive regulation of actin filament polymerization  T cell costimulation  receptor internalization  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  negative regulation of epidermal growth factor receptor signaling pathway  signal transduction in response to DNA damage  identical protein binding  regulation of MAPK cascade  insulin receptor substrate binding  poly(A) RNA binding  innate immune response  ephrin receptor binding  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  anatomical structure formation involved in morphogenesis  leukocyte migration  protein heterooligomerization  branching involved in labyrinthine layer morphogenesis  extracellular vesicular exosome  Grb2-EGFR complex  cellular response to ionizing radiation  positive regulation of reactive oxygen species metabolic process  
Ontology : EGO-EBIphosphotyrosine binding  SH3/SH2 adaptor activity  epidermal growth factor receptor binding  neurotrophin TRKA receptor binding  protein binding  nucleus  cytoplasm  endosome  Golgi apparatus  cytosol  plasma membrane  epidermal growth factor receptor signaling pathway  Ras protein signal transduction  cell-cell signaling  axon guidance  aging  blood coagulation  COP9 signalosome  insulin receptor signaling pathway  insulin receptor signaling pathway  fibroblast growth factor receptor signaling pathway  positive regulation of signal transduction  positive regulation of signal transduction  vesicle membrane  viral process  SH3 domain binding  protein kinase binding  protein phosphatase binding  platelet activation  positive regulation of actin filament polymerization  T cell costimulation  receptor internalization  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  negative regulation of epidermal growth factor receptor signaling pathway  signal transduction in response to DNA damage  identical protein binding  regulation of MAPK cascade  insulin receptor substrate binding  poly(A) RNA binding  innate immune response  ephrin receptor binding  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  anatomical structure formation involved in morphogenesis  leukocyte migration  protein heterooligomerization  branching involved in labyrinthine layer morphogenesis  extracellular vesicular exosome  Grb2-EGFR complex  cellular response to ionizing radiation  positive regulation of reactive oxygen species metabolic process  
Pathways : BIOCARTAEGF Signaling Pathway [Genes]    EPO Signaling Pathway [Genes]    Role of ERBB2 in Signal Transduction and Oncology [Genes]    Transcription factor CREB and its extracellular signals [Genes]    Growth Hormone Signaling Pathway [Genes]    Calcium Signaling by HBx of Hepatitis B virus [Genes]    IL 2 signaling pathway [Genes]    Insulin Signaling Pathway [Genes]    BCR Signaling Pathway [Genes]    The Co-Stimulatory Signal During T-cell Activation [Genes]    Inhibition of Cellular Proliferation by Gleevec [Genes]    Integrin Signaling Pathway [Genes]    p38 MAPK Signaling Pathway [Genes]    Trefoil Factors Initiate Mucosal Healing [Genes]    Role of Erk5 in Neuronal Survival [Genes]    Multiple antiapoptotic pathways from IGF-1R signaling lead to BAD phosphorylation [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]    Signaling of Hepatocyte Growth Factor Receptor [Genes]    Nerve growth factor pathway (NGF) [Genes]    PDGF Signaling Pathway [Genes]    Links between Pyk2 and Map Kinases [Genes]    Sprouty regulation of tyrosine kinase signals [Genes]    Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling [Genes]    TPO Signaling Pathway [Genes]    Bioactive Peptide Induced Signaling Pathway [Genes]    Fc Epsilon Receptor I Signaling in Mast Cells [Genes]    IGF-1 Signaling Pathway [Genes]    IL 4 signaling pathway [Genes]    Activation of Src by Protein-tyrosine phosphatase alpha [Genes]    Trka Receptor Signaling Pathway [Genes]    IL 3 signaling pathway [Genes]    IL 6 signaling pathway [Genes]    MAPKinase Signaling Pathway [Genes]    PTEN dependent cell cycle arrest and apoptosis [Genes]    T Cell Receptor Signaling Pathway [Genes]    CBL mediated ligand-induced downregulation of EGF receptors [Genes]    Erk1/Erk2 Mapk Signaling pathway [Genes]   
Pathways : KEGGMAPK signaling pathway    ErbB signaling pathway    Ras signaling pathway    Chemokine signaling pathway    FoxO signaling pathway    PI3K-Akt signaling pathway    Dorso-ventral axis formation    Osteoclast differentiation    Focal adhesion    Gap junction    Jak-STAT signaling pathway    Natural killer cell mediated cytotoxicity    T cell receptor signaling pathway    B cell receptor signaling pathway    Fc epsilon RI signaling pathway    Neurotrophin signaling pathway    Insulin signaling pathway    GnRH signaling pathway    Estrogen signaling pathway    Prolactin signaling pathway    Alcoholism    Hepatitis C    Hepatitis B    Pathways in cancer    Viral carcinogenesis    Proteoglycans in cancer    MicroRNAs in cancer    Renal cell carcinoma    Endometrial cancer    Glioma    Prostate cancer    Chronic myeloid leukemia    Acute myeloid leukemia    Non-small cell lung cancer   
Protein Interaction DatabaseGRB2
Wikipedia pathwaysGRB2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)GRB2
snp3D : Map Gene to Disease2885
SNP (GeneSNP Utah)GRB2
SNP : HGBaseGRB2
Genetic variants : HAPMAPGRB2
Exome VariantGRB2
1000_GenomesGRB2 
ICGC programENSG00000177885 
Somatic Mutations in Cancer : COSMICGRB2 
CONAN: Copy Number AnalysisGRB2 
Mutations and Diseases : HGMDGRB2
Genomic VariantsGRB2  GRB2 [DGVbeta]
dbVarGRB2
ClinVarGRB2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM108355   
MedgenGRB2
GENETestsGRB2
Disease Genetic AssociationGRB2
Huge Navigator GRB2 [HugePedia]  GRB2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneGRB2
Homology/Alignments : Family Browser (UCSC)GRB2
Phylogenetic Trees/Animal Genes : TreeFamGRB2
Chemical/Protein Interactions : CTD2885
Chemical/Pharm GKB GenePA28962
Clinical trialGRB2
Cancer Resource (Charite)ENSG00000177885
Other databases
Other databaseJackson Laboratory Mouse Genome Informatics Database; MGI: 99843
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineGRB2
iHOPGRB2
OncoSearchGRB2

Bibliography

C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains.
Clark SG, Stern MJ, Horvitz HR
Nature. 1992 ; 356 (6367) : 340-344.
PMID 1372395
 
The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling.
Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J
Cell. 1992 ; 70 (3) : 431-442.
PMID 1322798
 
A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos.
Olivier JP, Raabe T, Henkemeyer M, Dickson B, Mbamalu G, Margolis B, Schlessinger J, Hafen E, Pawson T
Cell. 1993 ; 73 (1) : 179-191.
PMID 8462098
 
An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.
Simon MA, Dodson GS, Rubin GM
Cell. 1993 ; 73 (1) : 169-177.
PMID 8462097
 
BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein.
Pendergast AM, Quilliam LA, Cripe LD, Bassing CH, Dai Z, Li N, Batzer A, Rabun KM, Der CJ, Schlessinger J
Cell. 1993 ; 75 (1) : 175-185.
PMID 8402896
 
The human GRB2 and Drosophila Drk genes can functionally replace the Caenorhabditis elegans cell signaling gene sem-5.
Stern MJ, Marengere LE, Daly RJ, Lowenstein EJ, Kokel M, Batzer A, Olivier P, Pawson T, Schlessinger J
Molecular biology of the cell. 1993 ; 4 (11) : 1175-1188.
PMID 8305738
 
Activation of the Ras signalling pathway in human breast cancer cells overexpressing erbB-2.
Janes PW, Daly RJ, deFazio A, Sutherland RL
Oncogene. 1994 ; 9 (12) : 3601-3608.
PMID 7970720
 
Mutant forms of growth factor-binding protein-2 reverse BCR-ABL-induced transformation.
Gishizky ML, Cortez D, Pendergast AM
Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (24) : 10889-10893.
PMID 7479904
 
Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein.
Fixman ED, Fournier TM, Kamikura DM, Naujokas MA, Park M
The Journal of biological chemistry. 1996 ; 271 (22) : 13116-13122.
PMID 8662733
 
Specific uncoupling of GRB2 from the Met receptor. Differential effects on transformation and motility.
Ponzetto C, Zhen Z, Audero E, Maina F, Bardelli A, Basile ML, Giordano S, Narsimhan R, Comoglio P
The Journal of biological chemistry. 1996 ; 271 (24) : 14119-14123.
PMID 8662889
 
A point mutation in the MET oncogene abrogates metastasis without affecting transformation.
Giordano S, Bardelli A, Zhen Z, Menard S, Ponzetto C, Comoglio PM
Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (25) : 13868-13872.
PMID 9391119
 
Growth hormone-induced tyrosine phosphorylation of EGF receptor as an essential element leading to MAP kinase activation and gene expression.
Yamauchi T, Ueki K, Tobe K, Tamemoto H, Sekine N, Wada M, Honjo M, Takahashi M, Takahashi T, Hirai H, Tsushima T, Akanuma Y, Fujita T, Komuro I, Yazaki Y, Kadowaki T
Endocrine journal. 1998 ; 45 Suppl : S27-S31.
PMID 9790226
 
Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation.
Cheng AM, Saxton TM, Sakai R, Kulkarni S, Mbamalu G, Vogel W, Tortorice CG, Cardiff RD, Cross JC, Muller WJ, Pawson T
Cell. 1998 ; 95 (6) : 793-803.
PMID 9865697
 
Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis.
Bardelli A, Basile ML, Audero E, Giordano S, Wennstrˆm S, Mˆİnard S, Comoglio PM, Ponzetto C
Oncogene. 1999 ; 18 (5) : 1139-1146.
PMID 10022119
 
Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7.
Yokouchi M, Kondo T, Houghton A, Bartkiewicz M, Horne WC, Zhang H, Yoshimura A, Baron R
The Journal of biological chemistry. 1999 ; 274 (44) : 31707-31712.
PMID 10531381
 
The gene structure of the human growth factor bound protein GRB2.
Bochmann H, Gehrisch S, Jaross W
Genomics. 1999 ; 56 (2) : 203-207.
PMID 10051406
 
GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex.
Carlier MF, Nioche P, Broutin-L'Hermite I, Boujemaa R, Le Clainche C, Egile C, Garbay C, Ducruix A, Sansonetti P, Pantaloni D
The Journal of biological chemistry. 2000 ; 275 (29) : 21946-21952.
PMID 10781580
 
Significance of the Grb2 and son of sevenless (Sos) proteins in human bladder cancer cell lines.
Watanabe T, Shinohara N, Moriya K, Sazawa A, Kobayashi Y, Ogiso Y, Takiguchi M, Yasuda J, Koyanagi T, Kuzumaki N, Hashimoto A
IUBMB life. 2000 ; 49 (4) : 317-320.
PMID 10995035
 
The role of membrane-associated adaptors in T cell receptor signalling.
Zhang W, Samelson LE
Seminars in immunology. 2000 ; 12 (1) : 35-41.
PMID 10723796
 
Up-regulation of the protein tyrosine phosphatase SHP-1 in human breast cancer and correlation with GRB2 expression.
Yip SS, Crew AJ, Gee JM, Hui R, Blamey RW, Robertson JF, Nicholson RI, Sutherland RL, Daly RJ
International journal of cancer. Journal international du cancer. 2000 ; 88 (3) : 363-368.
PMID 11054664
 
Disruption of T cell signaling networks and development by Grb2 haploid insufficiency.
Gong Q, Cheng AM, Akk AM, Alberola-Ila J, Gong G, Pawson T, Chan AC
Nature immunology. 2001 ; 2 (1) : 29-36.
PMID 11135575
 
Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis visualized in living cells.
Jiang X, Sorkin A
Molecular biology of the cell. 2002 ; 13 (5) : 1522-1535.
PMID 12006650
 
Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus.
Scaplehorn N, Holmstrˆm A, Moreau V, Frischknecht F, Reckmann I, Way M
Current biology : CB. 2002 ; 12 (9) : 740-745.
PMID 12007418
 
Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis.
Saucier C, Papavasiliou V, Palazzo A, Naujokas MA, Kremer R, Park M
Oncogene. 2002 ; 21 (12) : 1800-1811.
PMID 11896612
 
Actin-based motility: from molecules to movement.
Carlier MF, Le Clainche C, Wiesner S, Pantaloni D
BioEssays : news and reviews in molecular, cellular and developmental biology. 2003 ; 25 (4) : 336-345.
PMID 12655641
 
Met, metastasis, motility and more.
Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF
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Contributor(s)

Written05-2007Gagani Athauda, Donald P Bottaro
Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136 USA and Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA (GA) ; Urologic Oncology Branch, CCR, NCI, Bldg 10 CRC Rm 1-3961, 10 Center Drive MSC 1107, Bethesda, MD 20892-1107, USA (DPB)

Citation

This paper should be referenced as such :
Athauda G, Bottaro DP
GRB2 (Growth factor receptor-bound protein 2);
Atlas Genet Cytogenet Oncol Haematol. May 2007
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/GRB2ID386ch17q25.html

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