Question

Explore the role of phosphatases in the MAPK system

a) If the phosphatases in the cascade have very low activity

b) If the phosphatases in the cascade have very high activity.

Answer 1

MAPK or Mitogen activated protein kinase pathway is a mitogen induced pathway. so, this pathway helps proliferate a cell by mitosis. At first a mitogen binds with the receptor of a specific cell and activates the intracellular tyrosin kinase domain called receptor tyrosin kinase (RTK). The tyrosin residues of this RTK is phosphorylated and activates Ras-GEF(Ras guanine nucleotide exchanging factor) via adaptor protein Grb2. This Ras-GEF dissociates the GDP from Ras protein and converting it with GTP from the cytosol. This GTP bound Ras protein is the activated form to initiates the MAP kinase pathway. This activated Ras protein (Ras-GTP) then activates Raf in the plasma membrane. Raf activates Mek, Mek activates Erk protein. The Erk in turn phosphorylates different transcription regulatory protein for modulate the gene expression to proliferate the cell.

• Role of Phosphatases in the MAPK system:There is a enzyme present in that proliferating cell cytosol named phosphatase, this enzyme reverse the phosphorylation of RTK and inactivates the Ras protein in plasma membrane by hydrolyzing the bound GTP to GDP. This hydrolyzation of bound GTP to GDP of Ras protein and dephosphorylation of tyrosin residue causes to inactivates the MAP kinase pathway. This regulation by phosphatase is important to maintain the cell division and mitosis after a certain level.

a) If the phosphatases in the MAP kinase cascade, have very low activity then the dephosphorylation of tyrosin residue and hydrolyzation of GTP to GDP of Ras is become slow and decreased. This Decrease in Ras inactivation causes, longer duration of MAP kinase pathway. There is very low negative regulation of cell proliferation. Cell proliferate for much longer time, this will cause a undiserable growth of the cell and lead to form longer cell shape.

b) If the phosphatases in the cascade have very high activity, then the negative feedback to the MAP kinase pathway is also increased. The cell proliferation become stop before the final stage. This high level of phosphatase in the cytosol causes more rapid dephospharylation and hydrolyzation of bound GTP to GDP of Ras protein. This will cause rapid inactivation of MAPK pathway and results in short/less growth of the cell.