How does EGFR activate PI3K?
Mutated EGFR or ligand bound wild-type EGFR leads to PI3K/AKT activation. AKT phosphorylates Tiam1 at several serine/threonine sites and then facilitates its binding to 14-3-3. Tiam1 bound to 14-3-3 become stable and accumulates to promote high Rac1-GTP, which contributes to cell growth and proliferation.
Does Grb2 recognize EGFR?
Abstract. Adaptor protein Grb2 binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades.
What does binding of EGF to EGFR do?
The binding of the epidermal growth factor (EGF) to its receptor (EGFR) triggers a large set of downstream processes, ultimately causing cell growth, differentiation and proliferation (1,2). The receptor interaction and subsequent events are essential for the cell, although they may also be a threat to it.
What is EGFR RTK?
The epidermal growth factor receptor (EGFR) is often considered the “prototypical” receptor tyrosine kinase (RTK) and has been intensively studied. It is one of a family of four RTKs in humans, the others being ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4 (Fig.
Where is EGFR phosphorylated?
Ligand-activated EGFR undergoes autophosphorylation on multiple tyrosine residues, most of which are located in the C-terminal non-catalytic sequence; they include Y992, Y1068, Y1086, Y1148, and Y1173 [7,22–26].
What is another name for gefitinib?
Gefitinib, sold under the brand name Iressa, is a medication used for certain breast, lung and other cancers. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor (EGFR) in target cells.
What is the EGF pathway?
EGF/EGFR signaling pathway cascade. EGFR signaling pathway is one of the most important pathways in mammalian cells, which regulate a series of important events including proliferation, migration, differentiation, apoptosis, as well as those that regulate intercellular communication during development.
Where does EGF bind to EGFR?
EGF binding by EGFR occurs within the amino-terminal 622 amino acid extracellular region, which is divided into four domains, I–IV, also known as the L1, S1, L2, and S2 domains, respectively (Bajaj et al., 1987).
What is RTK pathway?
Receptor tyrosine kinases (RTKs) are a family of cell surface receptors, which act as receptors for growth factors, hormones, cytokines, neurotrophic factors and other extracellular signaling molecules.
What does phosphorylated EGFR do?
Introduction. Epidermal growth factor receptor (EGFR) is involved in regulating cell growth in breast carcinomas. Its activated form, phosphorylated EGFR (pEGFR), is correlated with poor prognosis in lung cancer, but it has not yet been fully investigated in breast cancer.
How does EGFR get phosphorylated?
The EGFR belongs to the family of receptor tyrosine kinases and activation by its ligands leads to trans-auto-phosphorylation at numerous tyrosine residues. The binding of adapter proteins can initiate diverse downstream signaling pathways such as MAPK, AKT or STAT signaling.
What is the molecular mechanism and site of action of SHP2?
However, the molecular mechanism by which SHP2 effects its biological function is unknown. In this report, we provide evidence that defines the molecular mechanism and site of action of SHP2 in the epidermal growth factor-induced mitogenic pathway.
What is the role of SHP2 inhibition in RTK-activated cancers?
SHP2 inhibition has demonstrated tumor growth inhibition in RTK-activated cancers in preclinica … Src homology 2 domain-containing phosphatase (SHP2) is a phosphatase that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and is required for full activation of the MAPK pathway.
Is tyr992 of the epidermal growth factor receptor a dominant SHP2 site?
We have identified Tyr992 of the epidermal growth factor receptor (EGFR) to be one such site, since its mutation to Phe renders the EGFR refractory to the effect of dominant-negative SHP2.