Receptors And Cell Signaling Flashcards
What are the two types of signals?
Water soluble
-hydrophilic
Lipid soluble
-hydrophobic
Epinephrine, insulin, and glucagon are examples of what time of signaling that initiates production of a second messenger, and has a shorter half life
Hydrophilic signaling
What are two receptors involved in hydrophilic signaling
G-protein couple receptors and receptor tyrosine kinase
Steroid hormones, thyroid hormones, and retinoids are examples of what type of signaling that binds to receptors proteins inside the cell and create a transcription factor from the molecule-receptor complex
Lipophlic signaling (hydrophobic)
Where can lipophilic signaling receptors be located
Cytosol or nucleus
_____ exist in an inactive complex with HSP90. Upon binding of signal, the HSP dissociates and the receptor complex translocates to the nucleus where it binds to a specific DNA sequence called the HORMONE RESPONSE ELEMENT in the promoter region
Cytoplasmic receptors
(Hydrophobic signaling)
*regulates transcription of genes
_____ receptors are already present in the nucleus and are bound to DNA awaiting for a signal to be activated
Nuclear receptors
-hydrophobic signaling
-regulates transcription of genes
Explain the structural motifs of G-Protein coupled receptors (GPCRs or 7TM receptors)
**heterotrimeric / hydrophilic
- extra cellular domain-binds to signal
- Transmembrane domain-composed of 7 alpha helixes
- Intracellular domain-interacts with G proteins
The intracellular domain of a GPCR activates the G protein by triggering what
Exchange of GDP—> GTP
An activated GTP-bound G protein interacts with a membrane-bound _________, usually producing a second messenger
Effector protein/ effector enzyme
Where is the GDP bound in inactive G proteins
To the alpha subunit which is attached To the beta and gamma subunits of the trimeric protein (has alpha, beta, and game subunits)
The activation of G proteins by exchange of GDP to GTP occurs via the action of _____
GEF
Guanine nucleotide exchange factor
*The GTP binds to the alpha subunit that then dissoates from the beta and gamma subunit of the trimeric protein
What is the function of intrinsic GTPase activity in G proteins? And what can accelerate its function?
Intrinsic GTPase activity returns the G protein to its inactive state by hydrolyzing the GTP to GDP
It can be accelerated by GTPase-activating protein (GAP)
7 simple steps of a G protein signal relay
- (Hydrophilic signal) ligand binds to GPCR
- Conformational change to GPCR
- GPCR able to interact and bind with the G protein inside of the cell
- Receptor than acts as a GEF and exchanges GDP for GTP
- Alpha subunit dissociates form other subunits
- Activated alpha subunit binds to activate or inhibit effector protein
- Effector molecule catalyzes reactions that produce secondary messengers, GTP hydrolyzes
Explain GPCR signaling via Gs pathway
- The activated GTP-bound alpha subunit activate adenylate cyclase (AC)
- AC converts ATP —> cAMP
- CAMP activates PKA
- PKA phosphorylates Target proteins and alters activity
Explain GPCR signaling via GI pathway
- Activated GTP-bound alpha subunit inhibits adenylate cyclase (AC) activity
- Inhibition of AC results in no cAMP production or activation of PKA
Explain GPCR signaling via the Gt pathway
- The primary signal comes from light (the g -protein is rhodopsin)
- Activated GTP-bound alpha subunit activates cGMP phosphodiesterase
- CGMP PDE converts cGMP—> 5’-GMP
- Important for vision
Explain the GPCR signaling pathway via Gq pathway
- Activated GTP-bound alpha subunit activates PLC which makes PIP
- PIP goes on to make DAG and IP3
- IP3 activates a calcium channel that release calcium from the ER/SR
- Release Ca2+ activates the Ca2+calmodulin-complex which then activates calmodulin dependent proteins
- DAG activates PKC which phosphorylates target proteins and alters activity
Epinephrine and histamine utilizes which specific GPCR pathway
Gs
Epinephrine/ norepinephrine and dopamine utilize what GPCR specific pathway
GI
Acetylcholine uses what GPCR specific pathway
Gq
Light signals use what GPCR specific pathway
Gt
What hormone can be administered to relieve bronchospasms during an asthma attack or to restore cardiac rhythms after cardiac arrest
Epinephrine
Which can follow a Gs or GI pathway
What is the function of cAMP phosphodiesterase
And cGMP phosphodiesterase
Hydrolyze cAMP -> AMP
Or hydrolyze cGMP -> 5’-GMP