Question

Gene expressions are regulated by various kinds of signals, which need to be transducted into the cell and regulate the transcription activator or repressor. Please describes the major pathways in signal transduction

Answer 1

Answer- Signal transduction is the chemical process which occur in the cell which converts external stimulus into a specific response and ultimately leads into the gene expression.

It starts with an external signal to a receptor and ends with cellular gene expression. Most signal transduction involves the binding of extracellular signaling molecule to the surface receptor.

Intracellular signaling is mainly carried by secondary messenger molecules like cAMP, Ca2+ and nitric oxide. These molecules initiate a cascade of reactions which ultimately leads into gene activation by acting as transcription activator.

These are the main pathways in signal transduction-

MAPK/ERK pathway -

1. That is (mitogen activated protein kinases) also called as (Extracellular signal transducing kinases) . This cascade reaction is activated by Extracellular ligand is epidermal growth factor (EGF) and their receptor called Epidermal growth factor receptor (EGFR).
2. When the EGF binds to EGFR it initiates the tyrosine kinase activity of the cytoplasmic part of the receptor.
3. it leads into the attachment of docking proteins such as GBR2 and this binds to GEF (guanine exchange factor) and later to SOS protein.
4. GBR2 - SOS complex helps in the recruitment of active RAS protein which is already binded with GTP.
5. RAS activates RAF protein and which ultimately leads to the recruitment of MEK and phosphorylates it and activates MAPK ,Now MAPK can regulate the gene activarion by regulating the transcription.

cAMP dependent pathway

1. G- protein coupled receptor (GPCR) binds to the external stimulus which can be various hormones like catecholamines, neuro transmitters and some protein hormones.
2. It triggers a conformational change in the GPCR which ultimately triggers G-protein , it has a specific binding site for GTP and ultimately binds to adenylate cyclase which is an enzyme that converts ATP into Cyclic-AMP.
3. It triggers the activation of PKA ( protein kinase A) once it is activated it leads to direct activation of Transcription regulator which ultimately leads into Gene activation.

IP3/DAG pathway

1. Phosphoinositide pathway(PI-3) binds to phosphotyrosine residues on the cytosolic domain of activated Receptor tyrosine kinases.
2. It catalyses the formation of PI 3,4,5- Triphosphates which acts as a docking site for various cascade proteins like PDK1 and PKB.
3. Active PDK1 causes phosphorylation of PKB. Fully activated PKB then dissociates from the plasmamembrane and phosphorylates its many target proteins and which ultimately acts as a nuclear transcription factor.