41) Some cancers are caused by the overexpression of receptor tyrosine kinases (

Question

41) Some cancers are caused by the overexpression of receptor tyrosine kinases (RTKs). Itis known that RTK signaling pathways commonly stimulate cell division. Why wouldthe overexpression of receptor tyrosine kinases lead to cancer development?

41)

A) If there are too many RTKs on the cell surface, this will tend to allow cells toadhere to each other. Once they adhere, RTKs from one cell can bind to RTKsfrom another cell, and they can activate each other leading to activation ofdownstream signaling pathways in both cells.

B) If there are too many RTKs on the cell surface, this will promote the inhibition ofautophosphorylation. In the absence of autophosphorylation, it is more likely thatthe RTK downstream signaling pathway will be active.

C) If there are too many RTKs on the cell surface, it is less likely that inhibitors willbind to all of the available RTKs and block their ability to enter the nucleus. As aresult, some of the RTKs will be able to enter the nucleus to stimulatetranscription.

D) RTKs are activated by dimerization, caused by ligand binding. If there are toomany receptors on the cell surface, it is possible that these receptors dimerize inthe absence of ligand binding, thus stimulating cell division at inappropriate times.

Explanation / Answer

Option D is correct. Receptor Tyrosine Kinases (RTK) are activated by dimerization, caused by ligand binding. RTKs are present as a monomer on the cell surface. When ligand (signals) comes to these receptor then the two RTKs combine and forms a dimer which causes RTKs activation by phosphorylation. In addition to this, it has been observed by the biochemical and kinetic studies of catalytic core of several RTKs that the oligomerization increases the concentration of the RTKs, leading to efficient transphosphorylation (two receptors phosphorylate each other) of tyrosine residues in the activation loop of the catalytic domain and activate the RTKs. Hence if there are too many receptors on the cell surface then occurance of transphosphorylation will increase and hence activation of RTKs will occur which regulate cell division.

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