Question

With the proto-oncogene hypothesis, which of the RTK mutations listed below are predicted to be oncogenic?

a. a complete deletion of the rtk gene

b. a deletion of rtk gene exon encoding the tyrosine kinase domain

c. a point mutation in the RTK kinase domain that resulted in an inability to bind ATP

d. a point mutation in the MTK kinase domain that locks the activation loop “on”

e. a small deletion in the regulatory region of the rtk gene that enhances RNA pol II binding

Answer 1

Answer: c. a point mutation in the RTK kinase domain that resulted in an inability to bind ATP

Explanation:

Proto-oncogenes are a group of genes that cause normal cells to become cancerous when they are mutated. Receptor tyrosine kinases (RTKs) are involved in mediating cell-to-cell communication and controlling a wide range of complex biological functions, including cell growth, motility, differentiation, and metabolism. A dysregulation of RTK signaling leads to cause many human diseases, most notably, cancers. Abnormal RTK activation in human cancers is mediated by four principal mechanisms i.e gain of function mutations, genomic amplification, chromosomal rearrangements, and autocrine activation.

RTKs are generally activated by receptor-specific ligands. Under normal physiologic condition growth factor ligands bind to extracellular regions of RTKs, and the receptor is activated by ligand-induced receptor dimerization. A gain of function mutation in an RTK leads to the production of constitutively active receptors, which transmit aberrant downstream signal in the absence of the normal ligands. In some cases, a point mutation changes a normal RTK into one that dimerizes and is activated even in the absence of ligand. These mutations hyperactivate the kinase and, subsequently, its downstream signaling, conferring oncogenic properties.

So the answer is “c. a point mutation in the RTK kinase domain that resulted in an inability to bind ATP”