Question

1. How are SH2 and SH3 domains important in the activation of Ras by receptor tyrosine kinases?

2. How is the regulation of the steady-state level of IP3 analogous to that of cAMP?

Answer 1

SH2 and SH3 are small protein modules that help in regulating protein protein interactions in signal transduction pathways that are activated by protein tyrosine kinase. SH2 role is binding to short phosphotyrosine containing sequence in growth factor receptor and other phosphoproteins.

SH3 role is binding to target proteins that contain proline and hydrophobic amino acids.

s is small GTP binding protein and its function is in signal transduction pathway used by growth factors to initiate cell growth and differentiation. So the growth factors induces Ras to to move from inactive GDP binding site to active GTP binding site.

SH2 and SH3 domain contaning proteins utilize SH2 and SH3 to link receptor and cytoplasmic protein tyrosine kinase to the Ras signalling pathway and to phosphotidyinositol hydrolysis. In this way SH2 and SH3 activate the Ras pathway which is essential for cell growth and differentiation.

2) IP₃ is essential for regulation of Ca²⁺ release. It is responsible for rapid mobilization of intracellular Ca²⁺ by increasing Ca²⁺ efflux from endoplasmic reticulum. cAMP increases the sensitivity of IP3 receptors to IP3, thereby potentiating the Ca²⁺ signals evoked by other receptors that stimulate IP3 formation.

So cAMP alone had no effect on intracellular Ca²⁺ stores but it increases the sensitivity of IP3. By adding cAMP accelerate Ca²⁺ release but it does not alter steady state level.