Solutions For An Introduction to Medicinal Chemistry Chapter 5 Problem 4Q

Figure: Signal transduction pathway from the growth factor to gene transcription

The growth factor binds to the binding site of tyrosine kinase receptor, which leads to the conformational change. Two dimers are formed after the dimerization of the enzyme and it is then followed by the phosphorylation, which adds the phosphate group to the active sites of the tyrosine kinase.

A signaling protein called Grb2 (growth factor receptor-bound-2) binds to a specifically phosphorylated site of the receptor-ligand complex and thus leading to its phosphorylation. Ras, a membrane protein then interacts with that receptor-ligand complex and functions like a G-protein with the exchange of GDP (guanosine diphosphate) to GTP (guanosine triphosphate).

This results in activation of the Ras protein. It activates the RAF, which is a serine-threonine kinase and further initiates a cascade of reactions. The activated RAF then activates MEK, which, in turn, activate the MAP (mitogen activated protein) kinases.

The map kinases phosphorylate and activate the transcription factor leading to the transcription of the genes into the nucleus. Hence, the signal amplification takes place at each stage where activation of a protein is caused due to several factors including binding of the ligand, phosphorylation, and activation of one protein causes the activation of another and so on.