Question

how can growth factors succeed in evoking many changes in the cell by binding and activating its receptors? and how deregulation of these proliferative programs lead to cell transformation?

where does Ras fit into this circuitry?

Answer 1

The growth factors are important part of the physiological part of the body as they are able to bind or act on specific receptors present on the cell surface. As they bind to these receptors, there is an activation of the signal and hence it leads the cell to start a cellular response through signal transduction process. The growth factor hence plays a very important role in activation of many pathways and hence affects the cellular growth. The growth factors also play a significant role in initiating and stimulating cell division and helps in starting signals that allows the cells to move through the cell cycle and undergo division. The regulatory program and functions as well as all the physiological process takes place through co-ordinate action of wide range of growth factors through the signaling pathway.

It is found in an experiment that involves the fibroblasts that when the serum derived growth factors are absent, they tend to irreversibly enter a starvation phase and go into non dividing stage. On exposing it to growth factors, it is found that the cell division starts synchronously due to important molecular changes. It is found that apart the transcription factors, there are group of many other proteins that are present in the cell which helps in transmitting the signals through the receptor on the cell surface. It was found that on addition of growth factors to the non-dividing or quiescent cells, it leads to many physiological changes due to the induction of the nuclear genes. Hence these growth factors help in channeling many signaling cascades.

The Ras growth factor or protein helps in conduction of many signaling pathways which are controlled by wide range of growth factors. These proteins affect cellular growth, differentiation and are known for initiating many pathways. As the growth factors bind to tyrosine kinase receptor, it tends to autophosphorylation and this is followed by its binding to GRB2 which recruits SOS or son of sevenless. The SOS is basically guanine nucleotide exchange factor that displace the GDP from Ras and enables binding of GTP. The Ras-GTP activates the Raf and this initiates a cascade of signaling pathway by phosphorylating MEK. The MEK phosphorylates ERK which subsequently phosphorylates Elk-1. Hence the Ras is an important factor important for activation of the MAPK/ERK kinase pathway.