Grb2 Family
Aliases: growth factor receptor-bound protein 2, SH2/SH3 adapter GRB2, Protein Ash, HT027, Adapter protein GRB2, abundant SRC homology, growth factor receptor-bound protein 3, epidermal growth factor receptor-binding protein GRB2, GRB2, MSTP084, NCKAP2, ASH, MST084, Grb3-3, EGFRBP-GRB2
Pfam Domain Structure
From GRB2 (human)
Members of the Grb2 Family
| 1: GRB2 » | Human | Mouse | Rat | Chicken | Fly | Worm |
| CMKB | GRB2 | Grb2 | Grb2 | GRB2 | drk | sem-5 |
| Entrez Gene | 2885 | 14784 | 81504 | 386572 | 36497 | 181055 |
| Uniprot | GRB2_HUMAN | GRB2_MOUSE | GRB2_RAT | GRB2_CHICK | DRK_DROME | SEM5_CAEEL |
| OMIM | 108355 | - | - | - | - | - |
| Reagents | - | 2 available | - | - | - | - |
| Results | 5 available | - | - | - | 3 available | - |
Family Summary
Grb2 is an adaptor protein with N- and C-terminal src homology 3 (SH3) domains and a central src homology 2 (SH2) domain. The SH2 domain can bind to phosphoTyr residues of receptors or other adaptor proteins, such as SHC. The SH3 domains bind the Ras exchange factor SOS, but can also bind to other adaptor proteins such as GAB1 and GAB2. Thus, Grb-2 is involved in activation of Ras but can also play a role in other signaling pathways in mammalian cells.
References
- Dharmawardana PG, Peruzzi B, Giubellino A, Burke TR, Bottaro DP. Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy. Anticancer Drugs 2006; 17:13-20 (PubMed)
- Feller SM, Lewitzky M. Potential disease targets for drugs that disrupt protein-- protein interactions of Grb2 and Crk family adaptors. Curr. Pharm. Des. 2006; 12:529-48 (PubMed)
- Johannessen LE, Pedersen NM, Pedersen KW, Madshus IH, Stang E. Activation of the epidermal growth factor (EGF) receptor induces formation of EGF receptor- and Grb2-containing clathrin-coated pits. Mol. Cell. Biol. 2006; 26:389-401 (PubMed)
- Natarajan K, Berk BC. Crosstalk coregulation mechanisms of G protein-coupled receptors and receptor tyrosine kinases. Methods Mol. Biol. 2006; 332:51-77 (PubMed)
- Sármay G, Angyal A, Kertész A, Maus M, Medgyesi D. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol. Lett. 2006; 104:76-82 (PubMed)
- Zarich N, Oliva JL, Martínez N, Jorge R, Ballester A, Gutiérrez-Eisman S, García-Vargas S, Rojas JM. Grb2 is a negative modulator of the intrinsic Ras-GEF activity of hSos1. Mol. Biol. Cell 2006; 17:3591-7 (PubMed)
Consortium Results & Data
Discovery» Drosophila Migration Genes
| Gene | Name | Function |
Cell Type |
Phenotypes |
Reagents/ Alleles |
Reference |
|
drk Entrez: CG6033 Flybase: FBgn0004638 |
Downstream of receptor kinase | signal transduction, adaptor | embryonic hemocyte | Loss of function: no zygotic phenotype | not clear what kind of allele: drkDP2 | Cho 2002 |
Discovery» wt-migratory_cells vs wt-non-migratory_cells
| Symbol | Description | Median Values | Fold Change | Probe ID |
|
drk Flybase Entrez CMCKB |
downstream of receptor kinase |
Mig: 83.8 Non-Mig: 51.1 |
1.63990 | 153747_at |
Discovery» Drosophila Morphology Genes
| Gene | Name |
Cell Count/ Normalization |
Stellate11 NumCorners |
Stellate22 Binsum6 |
Non-Spreading3 | |
|
CG6033 Entrez Gene: 36497 |
downstream of receptor kinase Aliases: Enhancer of sevenless-2B; downstream receptor kinase |
5.688 1.129 |
1.173 | 1.026 |
Actin: 0.849 Area: 1.129 Ratio: 0.752 |
|
Discovery» siRNA migration screen using a wound healing approach
| Gene | Description | MCF-10A phenotype | Secondary screen | Wound Image | Morphology | Time-lapse |
|
GRB2 Aliases: ASH, Grb3-3, MST084, MSTP084, EGFRBP-GRB2 Entrez Gene: 2885 siRNA catalog |
growth factor receptor-bound protein 2 mRNA: NM_002086 Library: MAR Classification: adaptor Focal Adhesion Related: Yes |
Final bin: Low Alamar - MC SMARTpool bin: Low Alamar Avg area: 4.05 Avg Alamar: 0.51 Knockdown %: not done |
ERBB2: No Change BCL2: Low Alamar |
 Link |
 Link |
Discovery» siRNA Focal Adhesion Phenotypes
| Gene | Description | High-Res | Montage |
|
GRB2 Aliases: ASH, Grb3-3, MST084, MSTP084, EGFRBP-GRB2 Entrez Gene: 2885 siRNA catalog |
growth factor receptor-bound protein 2 mRNA: NM_002086 Library: MAR |
 Link |
 Link |
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
| IPI | Locus | Description | CB Spectra | CB peptide | PD Spectra | PD peptide | ratio |
| IPI00021327 | GRB2 | GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2. | 3 | 2 | 3 | 2 | 1.00 |
Proteomics» Table 2. Proteins in major organelles and subcellular compartments
| IPI | Locus | Description | CB Spectra | PD Spectra | ratio | Location |
| IPI00021327 | GRB2 | GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2. | 3 | 3 | 1 | cytosol |
Discovery» Genes that increase migratory behavior in MCF-10A cells
| Protein | Protein Class |
BC-1000 cDNA |
mcf7/ mcf10a |
mcf7/ mcf10a-csf1r |
mcf7/ mcf-10a-csf1r_csf |
mcf7/ mcf10a-erbb2 |
|
GRB2 Entrez GeneID: 2885 CMKB Orthologs |
Signal transduction |
+++
|
Consortium Related Products*
Mice » activity page
| Ortholog | Species | Name | Method | Phenotype | Status | Jax Availability | Source | Publications |
|---|---|---|---|---|---|---|---|---|
| GRB2 | mouse | Grb2 - hypomorph | - |
Perinatal death due to cleft palate. | completed |
-
|
-
|
Saxton et al. |
| GRB2 | mouse | Grb2 | - |
Embryonic lethality at E4. Failure in endoderm differentiation. Chimeric embryos show that Grb2-null cells do not contribute to the epiblast. | completed |
-
|
-
|
Saxton et al., Cheng et al. |
* The resources presented here are largely those generated by the Consortium. The sidebar provides public databases that complement Consortium activities. For mice and biosensors, a public database is not available and therefore we have attempted to generate a migration related list for your convenience.
The primary classification of CMKB families is the homeomorphic family, whose members are both homologous (evolved from a common ancestor) and homeomorphic (sharing full-length sequence similarity and a common domain architecture).