Lecture 2 Flashcards
What does transmitting messages across the cell membrane involve?
conformational changes
What are second messengers
are chemical signals that are not embedded in the membrane and can diffuse in the cell to pass on the message
Give three reasons why 2nd messengers are are important chemicals for signal transduction
- only few receptors may be activated but each receptor produces many second messengers; this amplifies the signal
- 2nd messengers can often diffuse through the cell to other parts of the cell to influence different proteins
- multiple receptors can use common 2nd messengers allowing finely tuned regulation of cellular activity
What are the two common 2nd messengers
cAMP and Ca2+
What is the first 2nd messenger discovered
cAMP
by Earl Sutherland
Which enzyme makes cAMP
adenylate cyclase
true or false; cAMP are key components of GPCR signal transduction mechanisms
true
Describe the G protein cycle
- ) a hormone will bind to the receptor; receptor is activated
- ) the GDP of the alpha G protein will then be replaced by GTP
- ) the alpha G protein will dissociate from the beta-gamma dimer
- ) will attach itself to the adenylate cyclase; an effector; activating it to start producing cAMP from ATP
- ) the GTpase activity hydrolyses the GTP back to GDP thus eventually inactivating the G protein
- ) when the alpha G protein is inactivated, it will then reattach itself to the beta-gamma dimer once more
which enzyme does cAMP activate and what does it do?
cAMP activates protein kinase A (PKA); it is capable of phosphorylating many different proteins
What do you call a stimulatory G protein?
alpha GS
increases the production of cAMP
What do yo call an inhibitory G protein
alpha Gi
decreases the production of cAMP
What does PKA do?
cellular response
What is a kinase
catalyses the transfer of a phosphate group
true or false; phosphorylation can either inactivate or activate a protein
true
how does the cholera toxin affect the G protein?
- it permanently activates the G protein
- leading to excessive stimulatory adenylate cyclase and chronic elevation of cAMP levels
why does cholera cause non stop diarrhea
because cAMP in epithelial cells stimulate active transport of Na+
- small intestines epithelial cells and water from the mucosal surface of the epithelial cells into the lumen of the intestines
what happens when a hormone binds to the receptor (GPCR)
the receptor is activated by a hormone, which causes a conformational change in the receptor. This enables an interaction between receptor and G protein to occur
Why does GDP depart from alpha G protein when the hormone binds to the receptor
the conformational change resulting from the binding of the hormone from the receptor opens up the nucleotide binding site so that the GDP can depart and GTP from solution can bind in its place
- at the same time alpha subunit departs from beta-gamma dimer
true or false; a single activated receptor can stimulate nucleotide exchange between many G proteins, resulting in amplified response
true
true or false; the G protein is heterotrimeric
true
what controls phosphorylation
dephosphorylation by phosphotases
what enzymes catalyze phosphorylation
kinases
true or false; phosphorylation by kinases is an important mechanism for passing on messages in signal transduction processes
true
What does Ca2+ depend on?
the release of Ca2+ from the SR in the action of the Neuromuscular junction
Describe the steps for Ca2+ release in the cytoplasm
- ) hormone binds to the receptor in the cell membrane
- ) phospholipase C is activated
- ) PIP2 is hydrolyzed to IP3 and DAG
- ) IP3 is the actual second messenger
- ) IP3 diffuses in the cytosol to the ER where it stimulates the release of Ca2+
- ) a complex is formed between calmodulin and Ca2+
- ) the complex activates cytosolic protein kinase
What happens when DAG encounters PKC (protein kinase C)
it acts as a second messenger and activates PKC (which is responsible for Ca2+ channels; regulating Ca2+ flow in and out of the cell)
