EGF Signal Transduction Pathway

Summary

The EGF (Epidermal Growth Factor) signaling pathway plays a key role in cellular repair and growth. It begins when EGF molecules bind to the EGF receptor, causing receptor dimerization and phosphorylation. This activates downstream proteins such as GRB2, SOS, and RAS, which in turn trigger a cascade leading to cell growth and division. The pathway culminates in the activation of ERK proteins that stimulate gene expression for protein synthesis. To maintain cellular balance, the pathway is deactivated via phosphatases or intrinsic GTPase activity of RAS. Proper regulation is critical to prevent uncontrolled cell growth, such as in cancer.

Takeaways

• 😀 The EGF (Epidermal Growth Factor) signaling pathway is crucial for the growth and division of epidermal and epithelial cells in response to injury or damage.
• 😀 Epidermal cells are found on the skin, while epithelial cells line internal organs and structures.
• 😀 The EGF receptor consists of two monomeric units that only form a dimer when EGF molecules bind to them.
• 😀 Upon binding, EGF causes a conformational change that leads to dimerization, initiating the signal transduction process.
• 😀 The dimerization of the EGF receptor allows the C-terminal tails of the receptors to interact with each other and undergo cross-phosphorylation.
• 😀 Cross-phosphorylation of tyrosine residues on the receptor creates binding sites for adaptor proteins, such as GRB2.
• 😀 GRB2 binds to the phosphorylated receptor and recruits SOS, which activates the small G-protein RAS by exchanging GDP for GTP.
• 😀 Activated RAS triggers the RAF kinase, which in turn activates MEK (Mitogen-Activated Protein Kinase).
• 😀 MEK then activates ERK (Extracellular Signal-Regulated Kinase), which enters the nucleus to stimulate gene expression for cell growth and division.
• 😀 The EGF signaling pathway is terminated through the action of phosphatases, which dephosphorylate tyrosine residues, and through the intrinsic GTPase activity of RAS, which hydrolyzes GTP to GDP.

Q & A

What are the two main types of cells discussed in the transcript, and where are they located?

The two main types of cells discussed are epidermal cells, which are found on the skin, the largest organ of the body, and epithelial cells, which cover the internal surfaces of various organs and structures in the body.

What is the role of epidermal growth factor (EGF) in the body?

Epidermal growth factor (EGF) is a peptide molecule that is released when epidermal or epithelial cells are damaged. It acts as a primary messenger in the EGF signal transduction pathway, stimulating cell growth, division, differentiation, and proliferation.

How does the EGF receptor function before and after EGF binding?

Before binding EGF, the EGF receptor consists of two separated monomeric units. Upon EGF binding, these monomers dimerize, forming a dimer and undergoing conformational changes that activate the receptor’s tyrosine kinase domain.

What is the significance of the C-terminal tail in the EGF receptor?

The C-terminal tail of the EGF receptor contains tyrosine residues that are crucial for the phosphorylation process. Once the receptor dimerizes, the C-terminal tails move into the active site of the opposing monomer, where they are phosphorylated to create binding sites for other signaling proteins.

What happens during the cross-phosphorylation process in the EGF signal transduction pathway?

During cross-phosphorylation, the C-terminal tail of one EGF receptor monomer enters the active site of the opposing monomer, leading to the phosphorylation of tyrosine residues. This phosphorylation creates docking sites for adapter proteins like Grb-2, which then initiate further signaling.

What is the role of Grb-2 in the EGF pathway?

Grb-2 (Growth Factor Receptor Bound Protein 2) is an adapter protein that binds to the phosphorylated tyrosine residues on the EGF receptor. It serves as an anchor, recruiting other proteins, such as SOS, to propagate the signal.

How does the activation of SOS contribute to the signal transduction process?

SOS (Son of Sevenless) activates the small G-protein Ras by facilitating the exchange of GDP for GTP. This activation of Ras triggers downstream signaling pathways that lead to cell growth and division.

What is the function of the Ras protein in the EGF pathway?

Ras is a small G-protein that, when activated by SOS, binds to GTP. Once activated, Ras propagates the signal by activating other proteins like Raf, which initiate a cascade of phosphorylation events leading to cell growth and gene expression.

What role does the protein kinase MEK play in the EGF signaling pathway?

MEK (Mitogen-Activated Protein Kinase) is activated by Raf, and in turn, activates other kinases such as ERK (Extracellular Signal-Regulated Kinase). These activated kinases enter the nucleus and stimulate the transcription of genes responsible for protein production, leading to cell growth and division.

How does the EGF signaling pathway contribute to cell division and growth?

The EGF signaling pathway activates a series of kinases that ultimately lead to the expression of genes that produce proteins. These proteins are essential for building cellular structures, such as the cytoskeleton, and are critical for cell growth and division, especially in response to damage like cuts in the skin.