Module 3: Signaling Flashcards
What are the 3 steps in receptor-mediated signal transduction?
- Reception
- Transduction
- Response
_________ represent the largest family of proteins found in the human genome.
G-Protein Coupled Receptors
What are two examples of GPCRs?
Adrenergic (norepi) and Muscarinic (epinephrine)
_________ receptors bind acetylcholine but ARE GPCRs.
Muscarinic
Discuss the cycle of G-protein activation/deactivation:
G proteins are composed of 3 subunits (a, b, y)
a subunit: binds GDP and replaces it with GTP then dissociates from the other subunits
The GTP-bound G-protein is then able to interact with effector enzymes (adenylate cyclase, phospholipase C) activating or inactivating them
After a short time, thee a subunit of G-protein will hydrolyze the GTP to GDP.
After hydrolysis, the 3 subunits recombine thus completing the cycle
Second Messenger Systems:
Discuss the Adenylate Cyclase second messenger system:
- binding of first messengers to membrane receptors triggers either an increase or decrease in the activity of adenylate cyclase via membrane-bound G-proteins.
- G-proteins designated as G_s will have a stimulatory effect on adenylate cyclase (AC), while G_i proteins will inhibit the activity of AC
- Adenylate cyclase is a membrane-bound enzyme that converts ATP to cAMP.
- cAMP activates particular protein kinases which phosphorylate specific enzymes that produce the ultimate physiological response (eg. mobilization of glucose from glycogen)
- Epinephrine (a 1st messenger) can stimulate or inhibit the production of cAMP depending on whether it binds to a or b adrenergic receptors
- cAMP is broken down to AMP by enzymes known as phophodieterases (PDEs)
- The relative activity of AC and PDEs will determine the amount of cAMP in the cell. Inhibitors of PDEs can act to cause an increase in the amount of cAMP in the cell, making PDEs viable molecular targets for therapeutic intervention
Second Messenger Systems:
Discuss the Phospholipase C/Ca2+ system:
- Many receptors respond to neurotransmitters or hormones by activating a membrane-bound phospholipase known as phospholipase C.
- Like adenylate cyclase system, this system utilizes G-proteins (in this case G_q) to activate phospholipase C.
*** Activated phospholipase C subsequently cleaves membrane-bound PIP2 into IP3 and DAG (2ndary messengers)
- IP3 diffuses through the cytosol and binds to receptors on the ER, causing rapid release of Ca2+
- This increase in intracellular Ca2+ allows for the formation of Ca2+-calmodulin complex which is responsible for activating the complex dependent protein kinases
- DAG is nonpolar and lipid soluble.
- DAG activates membrane-bound protein kinase C
- Like adenylate cyclase, protein kinase C is responsible for activating target enzymes that lead to the cellular response
SUMMARY:
- first messenger binds to GPCR
- G-protein w/ GTP activates phospholipase C
- Phospholipase C cleaves PIP2 into IP3 and DAG
- IP3 activates release of Ca2+ from ER
- DAG activates protein kinase C
Which of the following is an activator for Protein Kinase C?
A. DAG B. Ca2+ C. cAMP D. Ca2+-Calmodulin E. A and B
E. A and B
Which of the following is an activator for Protein Kinase A?
A. DAG B. Ca2+ C. cAMP D. Ca2+-Calmodulin E. A and B
C. cAMP
Which of the following is an activator for calcium/calmodulin dependent kinases?
A. DAG B. Ca2+ C. cAMP D. Ca2+-Calmodulin E. A and B
D. Ca2+-Calmodulin
Discuss the receptor tyrosine kinases:
What are the 4 receptor tyrosine kinase domains?
What is a common example of receptor tyrosine kinases?
- Receptor tyrosine kinases (RTKs) are BOTH receptors and enzymes.
- Like GPCRs, these are membrane embedded proteins.
Receptor tyrosine kinase domains:
- an extracellular ligand binding domain
- a transmembrane domain
- an intracellular tyrosine kinase domain
- an intracellular regulatory domain
Receptor tyrosine kinases are DIMERS that can have each site occupied w/ phosphates (kinda like hemoglobin)
Example:
- insulin receptors belong to this class of proteins
- growth factors are also receptor tyrosine kinases
What are the 4 main types of receptor signaling?
- GPCRs
a subunit: binds GDP and replaces it with GTP then dissociates from the other subunits
- The GTP-bound G-protein is then able to interact with effector enzymes (adenylate cyclase, phospholipase C) activating or inactivating them
- After a short time, thee a subunit of G-protein will hydrolyze the GTP to GDP.
- After hydrolysis, the 3 subunits recombine thus completing the cycle
- Receptor Tyrosine Kinase (RTKs)
- RTKs are BOTH a receptor and enzyme
- membrane bound
- Dimers
- - Cytokine Receptors
- signaling molecules for the immune system
- all cytokines are peptides, proteins or glycoproteins
- 3 hormones (growth hormone, prolactin and erythropoietin) have receptors that have characteristics of cytokine receptors
* ** JAK STAT - Intracellular or nuclear receptors
- small hydrophobic molecules that bind to receptors inside the cell (eg. steroids and thyroid hormones)
What are the main differences between Adenylate cyclase and Phospholipase C?
Adenylate cyclase:
- activated by G proteins (epinephrine)
- converts ATP to cAMP
- cAMP activates kinases (mobilization of glucose from glycogen)
- cAMP is broken down to AMP by phosphodiesterases (PDEs)
- cAMP activity is determined by AC and PDEs
Phospholipase C:
- activated by G proteins
- phospholipase C cleaves PIP2 into IP3 and DAG
- IP3 binds to ER to release Ca2+
- DAG activates Protein Kinase C
- Ca2+-Calmodulin activates protein kinases
