Question

2. The following is a description of a signaling pathway initiated by receptor tyrosine kinases. Ligand → RTK → Sos → Ras → Raf → MEK → ERK → Transcription factor → Cell growth A. (3pts) Which of these steps indicates the protein is activated after a GTP exchange step? B. (3pts) Which of these proteins can be deactivated by phosphatases? C. (4pts) Describe a mutation that would cause Ras to be permanently "on"? Would this mutation lead to high or low levels of cell growth? D. (4pts) Describe a second mutation in a different protein (i.e. not Ras) that can reverse the effect of the mutation in Part B on the level of cell growth E. (4pts) Why are mutations in pathways like this commonly found in cancers?

Answer 1

A. Ras-GDP proteins, following activation of tyrosine kinase receptors (TRK) by growth factors (GF), are activated through GDP/GTP exchange. In such an active form they are able to bind and regulate many effectors proteins. Ras to Raf then to MEK is the step that indicates the protein is activated after a GTP exchange step

B. GDP to GTP phosphorylation reaction activates Ras to relay the signal downstream. Ras is the protein that can be deactivated by phosphatases. Activation of Ras is short lived since it is inactivated by phosphatases and GAPS.

c. A point mutation due to a single base substitution causes H or K or N Ras mutation. This causes the Ras protein to be permenantly on by attaching to GTP always by which getting activated to relay the signal downstream. It will increase the cell growth tremendously to result in malignant tumor and colon or pancreatic cancer.

D.

E. The mutations in pathways like this- Ras-Raf-MEK-ERK signaling pathway is commonly found in cancers. Because the transduction of signals in this pathway are required for a cell to decide whether to grow, and produce new cells. Hence the controlled pathway can produce cells in orderly manner. If there is mutation in the proteins involved, it causes unruly type of cell division which results in cancer.