BIO135 G-Protein Notes.txt
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Describe the structure of a G Protein-linked receptor (or G protein-coupled).
- Seven transmembrane spanning domains.
- Large cytoplasmic region that associates/activates with trimeric G proteins
Does the GPCR have intrinsic enzymatic activity?
What are 4 classic downstream targets of G Proteins that regulate different effectors?
- Adenylyl cyclases
- Ion channels
- Protein kinases
What are the basic subunits of a G protein?
alpha, beta, gamma
What about G proteins might explain highly specific responses?
What part of the G protein binds with GDP?
The alpha subunit
When activated, the beta/gamma complex can ___.
move and activate other targets.
What else provides specific signaling specifity?
- Cell-specific receptors, G isoforms, and effectors
- Amount of receptors, G isoforms, and effectors
- Organization of signaling cascades
- Accessory proteins
How do accessory proteins regulate G protein action?
They regulate the strength, efficiency, and specificity of the transmitted signal.
What are some examples of accessory proteins?
- GAP-43 - promotes GDP dissociation
- AGS3 - stabilizes G-alpha-GDP interaction
- Tubulin - directly transfers GTP to G-alpha
What are three types of accessory proteins?
- Activators of G protein signaling (AGS)
- Regulator of G protein signaling (RGS)
- Inhibitors of GDP dissociation
Describe activators of G protein signaling.
Can activate G proteins without the use of a receptor
Describe regulators of G protein signaling.
- Accelerate the GTPase activity of specific G-alpha subunits.
- Quick inactivation - hydrolysis
What is the typical end of a pathway?
What are other roles associated with G proteins?
- Golgi stability (alternative binding partners)
- Cell polarity in the fruit fly and nematode
- Neurite outgrowth and path-finding
What do G protein-linked receptors activate?
- Adenylyl cyclase
- Phospholipase C-beta
What effect does the activation of adenylyl cyclase typically have?
- Increase of cyclic AMP concentration in the cytosol.
- This rise activates PKA.
- PKA enters the nucleus and phosphorylates CREB.
- CREB recruits CBP, and both stimulate gene transcription.
What is produced from the hydrolysis of PIP2?
- inositol 1,4,5-trisphosphate (IP3) - releases Ca2+ from the ER
- diacylglycerol (DAG) - helps to activate PKC
Describe how GPCRs increase cytosolic Ca2+ and activate PKC.
- PLC-beta is activated by G protein (via alpha, beta/gamma, or both).
- Two messenger molecules, P3 and DAG, produced from hydrolysis of PIP2.
- IP3 releases Ca2+ from ER
- Ca2+ and DAG activate PKC
What other purpose does the release of Ca2+ serve?
Prevents polyspermy by creating fertilization envelope
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