A scientist observes a mutation in the transmembrane region of EGFR that eliminates its ability to be stabilized by binding interactions during dimerization after ligand binding. Which hypothesis regarding the effect of this mutation on EGF signaling is most likely to be correct?

a. EGF signaling cascades would be active for longer in the cell.

b. EGF signaling cascades would be active for a shorter period of time in the cell.

c. EGF signaling cascades would not occur.

d. EGF signaling would be unaffected.

Epidermal growth factor (EGF) signaling control various biologic responses such as proliferation, differentiation, cell motility, and survival.

These trans-membrane proteins are activated following binding with ligands such as epidermal growth factor (EGF).

b. EGF signaling cascades would be active for a shorter period of time in the cell.

EGFR is synthesized as a single-pass transmembrane protein which consists of an intracellular kinase domain separated by a single transmembrane domain.

EGFR is activated by ligand-induced dimerization of the receptor monomer, which brings intracellular kinase domains into close proximity.

An increasing number of diverse studies, however, demonstrate that EGFR is present as a pre-formed, yet inactive, dimer prior to ligand binding.

Upon ligand binding to the extracellular domain of EGFR, its transmembrane domains rotate or twist parallel to the plane of the cell membrane, resulting in the reorientation of the intracellular kinase domain dimer from a symmetric inactive configuration to an asymmetric active form.

a. EGF signaling cascades would be active for longer in the cell.

• EGF signaling cascades would be active for a shorter period of time in the cell.

c. EGF signaling cascades would not occur.

• The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation in mammalian cells.

d. EGF signaling would be unaffected.

• EGFR (epidermal growth factor receptor) is a protein on cells that helps them grow. A mutation in the gene for EGFR can make it grow too much, which can cause cancer.
• Effects of EGFR include initiation of DNA synthesis, enhanced cell growth, invasion, and metastasis.