Cellular signaling follows a cascade of events and has multi

Cellular signaling follows a cascade of events and has multiple points of regulation. Which of the following could be a reason(s) why a signalling cascade is interrupted, or turned off, once it has been turned \'on\"? The ligand is prevented from reaching the binding site a chemical modification occurred on serine, threonine, or tyrosine side chains to turn on/off proteins a protein gets tagged with an ubiqutin group and gets degraded a G-binding protein binds to a GTP molecule A, B and C only A and B only All of the above

Solution

ANS- E (A,B,C)

A)Cell signalling can be turned off by modulation of the number of functional receptors on the surface of cells. In many cases sensitivity of a cell to a particular growth factor can be down-regulated by endocytosis of its receptors.Modifying the activity of the receptors where they cannot bind ligand or form a receptor-ligand complex can also lead to downregulation of a signalling event.

B)Cell signalling intermediates are often subjected to regulation by chemical modification like phosphorylation, dephosphorylation, acetylation, methylation etc. It may include autophosphorylation of the intermediate to downregulate or turn off the signalling process. And in many cases the candidate amino acids are serine , threonine, tyrosine. Example- Thr141 phosphorylation regulates the kinetics of PKC downregulation in COS7 cells.

C)In some cases of cell signalling there are instances where it has been shown that ubiquitin mediated proteolysis of signalling intermediate leads to downregulation of the signalling event. Example- Ubiquitin mediated degradation of Src kinases to downregulate various signal transduction pathways.

D)G binding protein is a family of proteins that act as molecular switches. When these G proteins bind GTP they are in ON state and in GDP bound state they are switched OFF. Hence a signalling cascade would not be turned off if a GTP molecule binds to a G protein instead it would be turned ON.