signal transduction and secondary messengers mahmoud farhat
TRANSCRIPT
Signal Transduction and Secondary
MessengersMahmoud Farhat
What is Signal Transduction?
What are the Secondary Messengers involved in this process?
How do they work?
Signal Transduction
A basic process involving the conversion of a signal from outside the cell to a functional chemical change within the cell
Signal Transduction
A ligand specifically and reversibly binds to a receptor forming a complex
Once the ligand binds, secondary messengers are produced within the target cell
Signal Transduction
General features of signal transduction that are common to all:
1. Signal interacts with a receptor
2. The activated receptor interacts with machinery producing a secondary signal
3. A change in the metabolic activity of the target cell occurs
4. Transduction event ends and the cell returns to prestimulus state
G ProteinsG proteins bind GDP or GTP nucleotides
They are made up of three different subunits associated with the inner surface of the plasma membrane and transmembrane receptors, which are called G protein-coupled receptors (GPCRs)
Three subunits are:Gα – binds the nucleotidesGβ dimerGγ
G proteinsIn the inactive state, Gα has GDP in its binding
site
Ligand binds to GPCR causing a conformational change
GDP leaves and GTP binds activating Gα and causing it to dissociate from the GβGγ dimer
Activated Gα will then activate an effector molecule such as adenylyl cyclase – an enzyme that catalyzes the conversion of ATP to the secondary messenger cAMP
Secondary Messengers
Main classes of secondary messengers:Cyclic nucleotides (cAMP and cGMP)Inositol trisphosphate (IP3)Diacylglycerol (DAG)Calcium ions (Ca2+)
Cyclic Nucleotides
Cyclic AMP (cAMP)
Major secondary messenger used in many pathways of the body
Adenylyl cyclase, activated by a G protein, synthesizes cAMP from ATP
Some hormones that use cAMP:GlucagonLHAdrenaline
Cyclic Nucleotides
Protein Kinase A is a type of protein that is activated by cAMP
It is known as a cAMP-dependent protein kinase that phosphorylates target proteins to activate them
Cyclic Nucleotides
Cyclic GMP (cGMP)
Synthesized from GTP using guanylyl cyclase
Effects of cGMP are mediated through Protein Kinase G – a cGMP-dependent kinase that phosphorylates target proteins
cGMP serves as a secondary messenger for hormones such as ANP and nitric oxide
Inositol Trisphosphate and Diacylglycerol
IP3 and DAG are secondary messengers that are activated by G proteins
Hormones like ADH, TSH, and angiotensin or NTs like GABA bind to GPCRs and activate an enzyme called phospholipase C (PLC)
PLC then hydrolyzes a specific phospholipid known as phosphatidylinositol-4,5-bisphosphate (PIP2)
Hydrolysis of this phospholipid yields two products:Diacylglycerol (DAG)Inositol-1,4,5-trisphosphate (IP3)
DAG recruits Protein Kinase C – a calcium dependent protein kinase that phosphorylates target proteins
IP3 makes calcium available for activation of PKC
Calcium (Ca2+)
Calcium is one of the most important and widely used secondary messenger throughout the body
Muscle contraction
Presynaptic neuron