What are first messengers?
the extracellular signaling molecule-the ligand-that binds to the membrane receptor, e.g., epinephrine, hormones
What are second messengers and 2 examples of second messengers?
involved in signaling pathways they are small, non-protein, water-soluble molecules or ions, e.g., cyclic AMP and calcium
What is signal amplification?
elaborate enzyme cascades, in each step the cascade the number of activated products is much greater
How does signal amplification benefit the cell?
elicits a coordinated response and can release hundreds of millions of molecules
What is the role of phosphorylation cascades in signal amplification?
activated kinase activates a different kinase and so on, at each step more and more enzymes are recruited
Where are the receptors involved in cell signaling located?
in the plasma membrane, e.g., an internal membrane protein OR an intracellular receptor, e.g., steroid hormone receptors
What is the product of adenylyl cyclase?
How is adenylyl cyclase activity regulated?
the enzyme is modulated (positively or negatively) by different G proteins; intracellular cAMP levels go up or down depending on the summation of all the positive and negative signals on that cell
What reactions do protein kinases catalyze?
phosphorylation reactions: covalent transfer of phosphate group from ATP to specific amino acids of target cells, acts as an on or off switch for the target protein
What is the role of cAMP-dependent protein kinase in cell signaling?
to catalyze phosphorylation reactions
What reactions do phosphatases catalyze?
remove the phosphate groups
What are the subunits of Protein Kinase A?
2 regulatory subunits and 2 catalytic subunits
What is the subunit composition of the active enzyme?
in the cytoplasm cAMP binds to the R subunit, R2C2 dissociates into an R dimer and 2 C monomers, C monomers catalyze phosphorylation reactions
What is the subunit composition of the inactive enzyme?
Summarize the steps of the G protein cycle.
1. An activated receptor interact with the G protein, GTP replaces GDP on the alpha subunit, the G protein dissociates into alpha-GTP and a By dimer, the G protein is now on.
2. Activated G proteins interact with their target enzymes or ion channels.
3. An intrinsic GTPase activity of the alpha subunit hydrolyzes GTP to GDP, alpha-GDP and the By dimer reassociate inactivating the G protein.
What are examples of types of G proteins?
Gs - stimulatory G protein - stimulates adenylyl cyclase
Gi - inhibitory G protein - inhibits adenylyl cyclase
Golf - olfactory G protein
Gt - transducin, the G protein invovled in vision
What are the subunits of G proteins?
alpha,beta, and gamma
What would happen if the G protein cycle is disrupted by mutations? (loss of function mutations)
prevent formation of stable mRNA or protein
What would happen if the G protein cycle is disrupted by mutations? (gain of function mutations)
e.g., activation of receptor in the absence of agonist