Question

7a) Outline the two major cellular process/pathways activated by binding of EGF binding to the EGF-receptor within cells?

b) Signal transduction during cell signaling events frequently involves the action of kinases and phosphatases. Describe how these proteins function to regulate the action of individual proteins.

Answer 1

EGFR(Epidermal growth factor receptor) is a member of family Receptor tyrosine kinases (RTK) and also known as the Erb1/HER1. The EGF/EGFR signaling pathway induces cell proliferation, cell differentiation and cell survival. Two major intracellular signalling pathways activated by binding of EGF to EGFR are: RAS-RAF-MEK-MAPK  pathways which controls the progression of cell cycle from G1 phase to S phase, thus responsible for cell proliferation and PI3K-Akt pathway which aids in cell survival by activating anti-apoptotic and prosurvival signals.

RAS-RAF-MEK-MAPK: Binding of ligand EGF to EGFR causes it dimerisation and activation of intrinsic kinases which causes autophosphorylation of EGFR at tyrosine residues. A cytoptlasmic adaptor protein Grb2 binds to activated tyrosine and Grb2 further recruits SOS which then causes GDP-GTP exchanges in GTPase Ras. Ras-GTP molecule activates RAF which further activated MEK by its phosphorylation. MEK further phosphorylate MAPK(Microtubule associated protein kinase) and this MAPK is resposible for promoting cell growth by activating various transcriptional regulator.

PI3K-Akt: Binding of ligand EGF to EGFR causes its dimerisation and activation of intrinsic kinases which causes autophosphorylation of EGFR at tyrosine residues. A cytoplasmic adaptor protein Grb2 binds to activated tyrosine residues and Grb2 recruits PI3K to the cell membrane where it phosphorylates Phosphatidylinositol-4,5-bisphosphate(PIP2) to Phosphatidylinositol-3,4,5-trisphosphate(PIP3). PIP3 then recruits the protein kinase PADK1 which phosphorylate Akt and Akt in turn regulates the various anti-apoptotic and prosurvival proteins responsible for Cell survival.

2. Protein kinases and phosphatases are enzymes which are responsible for regulation of activity of various proteins during signal transduction pathways. The function of kinases is to activate the various signalling proteins by their phosphorylation. While the function of phosphatases are reverse of kinases, they inactivate the signalling proteins by dephosphorylating them which cause the conformational changes and bring them in inactive state.

EGF EGFR dimes Z (Play Sos (Grb Grb2 - FEB MBA cu Sterivad Cell Survival (MAPK) Cell proliferation