Compare and contrast receptor tyrosine kinase (RTK) signaling pathways such as the EGF–Ras–MAPK pathway with serine/threonine kinase (S/TK) signaling pathways such as the TGF? pathway with respect to (a) receptors, (b) phosphorylation targets,

Question

(c) signal transduction from the plasma membrane through the cytoplasm to the nucleus, and (d) effects on gene regulation.
What will be an ideal response?

Answer 1

Answer:
a) A single RTK contains a cytoplasmic kinase domain that autophosphorylates when primary signal bonding dimerizes the receptor. S/TK receptors that bind the primary signal associate with separate kinases that phosphorylate the ligand-binding receptor, which then binds to an activating protein.
b) In both cases, the receptors get phosphorylated. Downstream targets include the Raf–MEK–MAPK cascade kinases and transcription factors for the EGF–Ras–MAPK pathway and R-Smad for the TGFβ pathway.
c) RTK recruitment of GRB2 and the Ras–GEF Sos to the membrane activates Ras, which then activates Raf to initiate the Raf–MEK–MAPK cascade. This cascade amplifies the cytosolic signal and phosphorylates MAPK, which moves into the nucleus and phosphorylates transcription factors. In the TGFβ pathway, phosphorylation of R-Smad promotes complex formation with Smad4. This complex moves into the nucleus.
d) MAPK phosphorylates transcription factors, activating them to turn on specific genes. In the TGFβ pathway, the Smad complex associates with other cofactors and DNA-binding proteins to regulate gene expression.