Signal transduction is critical because...
Allows organism to sense its environment and formulate a biochemical response
5 Steps of the Signal transduction pathway
Release of a primary message
Relay - secondary messengers
A low [ ] of signal in the environment (outside) can yield a.....
Large intracellular signal and response (inside)
What are the 3 major classes of membrane receptors?
Seven-transmembrane helix (7TM) receptors associated with heterotrimeric G-proteins
Dimeric membrane receptors that recruit protein kinases
Dimeric protein receptors that are protein kinases (both receptor and kinase functions)
The most common receptors in signaling events are?
7TM receptors have a host of functions!
They mediate hormone action, secretion, neurotransmission, chemotaxis, exocytosis, control of blood pressure, embyrogenesis, cell growth, development, smell, taste, vision, viral infection
Several thousand 7TM receptors exist. What % of currently used drugs target these receptors?
7TM receptors have _________ and ___________.
Seven alpha-helices and span the membrane bilayer
Ligand epinephrine receptor binds to B-adrenergic receptor. What happens? Why?
Change in conformation to allow the signal to be able to be detected inside the cell
The unactivated G-protein is a heterotrimer consisting of...
An alpha subunit, bound to GDP and beta and gamma subunits.
After binding epinephrine, the beta-adrenergic receptor activates a...
*NOTE: One receptor can stimulate many G-proteins*
Once G-protein is activated, the alpha subunit exchanges...
GDP (low energy state) for GTP
The exchanged GTP bound alpha-subunit transmits the signal to other cellular components which...
Gives an amplified response/keeps amplifying the signal
The activated G-protein will then stimulate...
Activation of adenylate cyclase leads to...
Synthesis of cAMP
Binding of epinephrine to the receptor on the cell surface _______ the rate of cAMP production in the cell.
cAMP stimulates phosphorylation of many target proteins, including...
Protein Kinase A which controls many responses (GIT, blood, skin, etc.)
Protein Kinase A (PKA) has...
2 regulatory subunits and 2 catalytic components
Binding of cAMP dissociates which subunits of the PKA?
How do you turn this epinephrine signal off? (3 ways)
G alpha has ability to reset itself by cleaving the bound GTP to GDP to terminate the G-protein
cAMP phosphodiesterase converts cAMP to AMP which prevents activation of PKA
The epinephrine-beta-adrenergic receptor is reversible. Dissociates/resets
What is Cholera?
Produces a toxin that modifies one specific G-protein and locks it in the active form. Net result is a loss of NaCl and water into the intestine
*Severe diarrhea that can kill you within 24 hours
Pertussis Toxin (Whooping Cough)
Modifies a G-protein by trapping it in the inactive form so you cannot turn on a signaling pathway so it is rendered inactive
Hydrolysis of Phosphatidylinositol Biphosphate by Phospholipase C generates 2 secondary messengers
DAG and IP3
Binding of IP3 in the ER causes what? What is an example of this pathway?
Release of Ca2+ out of the ER and raise how much calcium is present in the cytoplasm
Ex: Vasopressin binding to a 7TM
DAG with calcium activates...
Protein kinase C
The human growth hormone will bind to a receptor and causes it to...
Dimerize which results in the turning on of JAK2 and they phosphorlate each other, which turns on kinases that then phosphorylate other targets.
Describe the pathway of this receptor.
What does it lead to?
Forms dimers that lead to cross-phosphorylation and activation of two intracellular kinase domains.
Leads to activation of Ras, which turns on specific targets that activate growth
One molecule - no separate kinase involved
Ras is a key component of...
The EGF pathway
Ras is a member of the family of small ______, which control a variety of cellular processes.
Active when bound to ____ and inactive when bound to ____.
G proteins or GTPases
The hormone insulin is secreted when...
Blood glucose levels are high
Insulin receptor is an...
The RTK dimers form on insulin binding and phosphorylate to turn on and activate a series of molecules that leads to the activation of the kinase ______.
AKT which phosphorylates glucose transporter GLUT4, increasing glucose uptake by the cells and enzymes that convert glucose into glycogen.
Insulin signaling is turned off by...
Action of phosphotases removing phosphates from activated proteins in the insulin pathway ("Timers")
What is calmodulin?
Ca2+ sensor with 4 calcium binding sites called EF hands and activates targets such as pumps.
Too much or mutated RTK or Ras can lead to...
What is an oncogene?
A mutated proto-oncogene leading to unrestrained growth
Control cell growth
What may be an effective anti-cancer drug and why?
CML (Leukemia) can be caused by overexpression of a tyrosine kinase, if inhibited, growth would be stunted.
Negative free energy will always be...