Question

Compare and contrast the EGFR and insulin receptor pathways with regard to activation of upstream signaling proteins on the cytosolic side of the plasma membrane.

Short answer

Question: Compare and contrast the activation of upstream signaling proteins on the cytosolic side of the plasma membrane in the EGFR pathway and insulin receptor pathway. Answer: Both EGFR and insulin receptor pathways involve ligand binding, receptor dimerization, and autophosphorylation of tyrosine residues in their activation process. However, they differ in their respective ligands (EGF for EGFR and insulin for the insulin receptor) and the downstream signaling proteins they recruit. The EGFR pathway recruits Grb2, activating the MAPK cascade and is involved in cell proliferation, differentiation, and survival, while the insulin receptor pathway recruits IRS proteins, activating the Akt signaling pathway and regulating glucose uptake, metabolism, and cellular growth.

Step-by-step solution

Introduction to EGFR and Insulin Receptor Pathways

Both EGFR and insulin receptor pathways are essential for cell growth and metabolism regulation. They are receptor tyrosine kinase (RTK) pathways, which involve ligand binding and autophosphorylation of tyrosine residues in their activation process.

Identifying the activation process of EGFR pathway

The EGFR pathway is activated when an epidermal growth factor (EGF) ligand binds to its extracellular domain. This interaction triggers the dimerization of two EGFR molecules, causing a conformational change that enables the activation of its intrinsic kinase activity. Autophosphorylation of tyrosine residues in the intracellular, cytoplasmic region takes place, which then serves as docking sites for recruiting downstream signaling proteins like Grb2. Grb2 further binds to the protein SOS, which ultimately leads to the activation of the MAPK cascade, triggering downstream signaling events that include cell proliferation, differentiation, and survival.

Identifying the activation process of the Insulin Receptor Pathway

The insulin receptor pathway is activated when insulin binds to its corresponding receptor, causing the two αβ receptor subunits to phosphorylate each other on tyrosine residues. This autophosphorylation event enables the activated insulin receptor to recruit downstream signaling proteins such as the insulin receptor substrates (IRS) proteins. The phosphorylated IRS proteins then serve as binding sites for the regulatory subunits of the PI3K protein, which activates the Akt signaling pathway, ultimately leading to regulation of glucose uptake and metabolism, as well as cell growth and survival.

Comparing the activation processes

Both EGFR and insulin receptor pathways involve ligand binding, receptor dimerization, and autophosphorylation of tyrosine residues. However, the ligands (EGF for EGFR and insulin for the insulin receptor) and their downstream signaling proteins (Grb2 in EGFR and IRS proteins in the insulin receptor pathway) differ.

Contrasting the downstream signaling proteins

Even though both pathways have common features in their activation processes, the downstream signaling proteins they recruit are different. The EGFR pathway recruits Grb2, which activates the MAPK cascade and is involved in cell proliferation, differentiation, and survival. On the other hand, the insulin receptor pathway recruits the IRS proteins, which activate the Akt signaling pathway, regulating glucose uptake, metabolism, and cellular growth.

Concluding the comparison and contrast

In conclusion, the EGFR and insulin receptor pathways are both receptor tyrosine kinase pathways with similarities like ligand binding, receptor dimerization, and tyrosine autophosphorylation. However, they differ in their ligands, recruited downstream signaling proteins (Grb2 in EGFR and IRS proteins in the insulin receptor pathway), and the biological processes regulated (cell proliferation and differentiation in EGFR, glucose uptake, and metabolism in the insulin receptor pathway).