Activation of the G-proteins leads to the generation of what 3 “second” messengers?
- cAMP
- DAG
- IP3
G-Protiin coupled receptors are the most numerous class of receptors with more than ___ members
140
What are 4 examples of non-endocrine signals that also act via G-Protiens?
- Glutamate
- Thrombin
- Odorants
- Photoreceptors
What are some examples of G-Protein coupled RECEPTORS?
TRH, GNRH, LH, FSH, TSH, oxytocin
How many times does the G-protein receptor cross the transmembrane domain? What is their shape?
7 times, alpha-helices
What do the 7 transmembrane alpha-helices form?
a pore
What do G-Proteins use as a switch? Which one activates it and which deactivates it?
GTP/GDP
GTP bound = G protein on
GDP bound = G protein off
When the G-Protein is ‘on’, what happens?
It moves along and activates adenylate cyclase and/or phospholipase C
What type of structure so G proteins have?
Trimeric
- Alpha subunit
- Beta subunit
- Gamma subunit
Which two G-Protein subunits bind together to form heterodimers?
Beta and Gamma subunits
What are the two different functional units of G-proteins?
- G-alpha
2. G-beta/gamma dimer
What happens to the G-protein functional subunits when GTP –> GDP?
G-alpha (carries the GDP/GTP) is displaced from G-beta/gamma dimer
- G(s)alpha:
- G(i)alpha:
- G(q)alpha:
- G(o)alpha:
- activates adenylate cyclase
- Inhibits adenylate cyclase
- activates phospholipase C
- activates ion channels
Is it that 1 hormone uses 1 G-protein, or can it use more than 1?
may use more than 1
Under what two conditions may G-protein use change?
- during development
2. depending on the concentration of the hormone or in different tissues
What happens in terms of G-protein function in some with the McCune Albright syndrome? What are 2 side effects?
Gain of G(2)alpha function: G-signaling pathway is on despite the absence of a hormone stimulant.
- Skin pigmentation (cafe au lait)
- breast development
- precocial puberty associated with ovarian cysts
What happens endocrinologicaly to someone who has Familial male precocious puberty?
High testosterone is produced by Lydia cells despite the absence of LH and FHS –> cells act autonomously
How many isoforms does Adenylate cyclase have? How do they differ?
> 10 - differ in their interactions with G-proteins
How many membrane spanning domains are adenylate Cyclades made up of? How many cytoplasmic domains do they have?
2 sets of 6 membrane spanning domains
2 cytoplasmic domains
What enzyme converts ATP to cAMP?
adenylyl cyclase
What amino acids of CREB does PKA phosphorylate?
serines and threonines, activating it
What does CREB stand for?
cAMP-response element binding protein
What is CREB?
a transcription factor which switches on genes by binding to the CRE sequence (enhancer sequence) of DNA to induce transcription of cAMP-inducible genes
How is the PKA signal terminated?
Phospho-diesterases hydrolyse cAMP to 5’AMP – this removes the cAMP from the regulatory subunits allowing them to bind back to PKA and inactivate it
