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GRB2 Gene Editing 
Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein without intrinsic enzymatic activity, which is widely expressed in all eukaryotic cells. It was originally discovered as epidermal growth factor receptor (EGFR) interacting protein, but is now known to form complexes with a wide variety of cellular proteins including, but not limited to, receptor tyrosine kinases, protein tyrosine kinases, phosphatases, adaptors and intracellular scaffolds.
The mature Grb2 is a 217 amino acid sequence consisting of one Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. It acts as an intermediate between cell-surface activated receptors and downstream targets through SH2 and SH3 domains. The Grb2 through a 100 amino acid sequence SH2 domain recruits many phosphotyrosine (pTyr) residues including receptor tyrosine kinases (RTKs), e.g. epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (HGFR), platelet-derived growth factor receptor (PDGFR), etc., non-receptor tyrosine kinases, such as BCR-ABL, insulin receptor substrate 1 (IRS1) and focal adhesion kinase (FAK). The SH2 domain promotes the activation of extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) cascade, which is mandatory for intracellular processes, such as cell growth, differentiation, protein trafficking and migration. The SH3 domain, a sequence of about 50 amino acids, interconnects Grb2 with son of seven-less (SOS) through the N-terminus (nSH3) and to a proline-rich sequence in SOS via the C-terminus (cSH3). The binding of the nSH3 domain with SOS generates the activation of two sets of protein actions, first guanine nucleotide exchange factors (GEFs) stimulation, which leads to the exchange of bound GDP to fresh GTP from the cytosol, and secondly GTPase activating proteins (GAPs) on Ras, which leads to the activation of GDP bound state. Ras becomes active when bound to GTP while they are inactive when bound to GDP. Therefore, activation of Ras triggers the stimulation of Raf, ERK, and MAPK cascade.
Figure 1. A model of Grb2 signaling pathway. (Ahmed Z, et al., 2015)
In fact, aberrant activation of the Grb2 through cell surface growth factor receptors is the main reason of diverse tumor evolutions. For example, the EGFR and the HER2/erbB-2 are the main factors in Grb2-intervened abnormal signaling, which leads to breast cancer occurrence. Similarly, HGF causes Grb2-mediated liver irregularities. In the case of a chronic myelogenous leukemia, the Grb2 through a SH2 motif forms direct complexes with BCR portion of the BCR-ABL gene. Likewise, a Grb2-regulated MAPK pathway abnormal proximity was observed in several cancers, including lung adenocarcinoma, gastric cancer, bladder cancer, colorectal carcinoma, etc. Therefore, extensive Grb2 cancer-affiliated concerns broaden the significance of this adaptor protein in the clinical arena. Targeting the Grb2 linkage to receptor tyrosine kinases, namely the EGFR through the Grb2-SH2 domain or to downstream signaling by marking the Grb2-SH3, the SOS motif might act as attractive Grb2 inhibitors. HAGBP is such a peptide molecule owing a strong ability to cross the membrane barrier and target the Nterminal SH3 domain of the Grb2 and disrupt the MAPK activity in CML in vitro. Another method is to use a cell permeable linker to assure the cell penetration of peptides. Similarly to peptidimer-c, a peptidimer was conjugated with a penetratin. The resultant peptidimer-c could cross cell membrane and bind both terminals of the Grb2-SH3 and inhibit proliferation in K562 cells in vitro.
GRB2 Gene Editing Services
CRISPR/Cas9 PlatformCB at Creative Biogene is dedicated to offering comprehensive CRISPR/Cas9 gene editing services and products for academic research, biotech research and pharmaceutical drug discovery. With deep gene editing knowledge and extensive experience in experimental operation and data processing, we help you effectively control GRB2 genes knockout/knockin/point mutation in cells or animals via CRISPR/Cas9 technology.
| Service | Details | Alternative cell lines or animal species |
| GRB2 Gene Editing Cell Line Generation | gRNA design and synthesis Transfect the cell lines you're interested Select the high expression cells and sort monoclonal cell Validate the knockout/knockin/point mutation of GRB2 by PCR and sequencing Provide cryogenically preserved vials of stable cells and final reports | HEK239T, Hela, HepG2, U87, Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc. |
| GRB2 Gene Editing Animal Model Generation | GRB2 gene conventional knockout animals GRB2 gene conditional knockout animals GRB2 point mutation animals GRB2 knockin animals | Mouse, rat, rabbit, zebrafish, C. elegans, etc. |
Related Products at CRISPR/Cas9 PlatformCB
| CATALOG NO. | PRODUCT NAME | PRODUCT TYPE | INQUIRY |
| CLKO-1676 | GRB2 KO Cell Lysate-HeLa | Knockout Cell lysate | Inquiry |
| CSC-RT1827 | GRB2 Knockout Cell Line-HeLa | Pre-Made Knockout Cell Line | Inquiry |
References
- Belov A A, Mohammadi M. Grb2, a double-edged sword of receptor tyrosine kinase signaling. Science signaling, 2012, 5(249): pe49-pe49.
- Ijaz M, et al. The role of Grb2 in cancer and peptides as Grb2 antagonists. Protein and peptide letters, 2017, 24(12): 1084-1095.
- Ahmed Z, et al. Grb2 monomer–dimer equilibrium determines normal versus oncogenic function. Nature communications, 2015, 6(1): 1-11.
- Ye Z, et al. GRB2 enforces homology-directed repair initiation by MRE11. Science Advances, 2021, 7(32): eabe9254.