Signal transduction Flashcards
3 parts of a simple information transfer system?
Primary signal, target, transducer system
How does hormone signaling work?
Hormone travels through blood until it reaches target cell, then binds to cell surface receptor, triggering responses
What are two common types of cell surface receptors?
G protein coupled receptors, Receptor tyrosine kinases
What do second messengers do? Name 4.
Act to modulate enzymes and amplify signal, typically via cascade. cAMP, cGMP, Ca 2+, IP3
How do heterotrimeric G proteins work?
G(abg) trimer is nonsignaling state. Attached to membrane by lipidation.
Activated GPCR makes G(abg) dissociate into G(a) and G(bg), accompanied by GDP/GTP exchange on G(a). G(bg) has no catalytic activity.
G(a) and G(bg) activate enzymes that generate second messengers.
GTP hydrolysis by G(a) = off mechanism, makes G(a) and G(bg) reassociate.
G(s) = inactive state. G(i) = active.
What is adenylate cyclase?
GPCR second messenger system. Converts ATP to cAMP.
Activated G(a)/GTP controls adenylate cyclase activity. G(s) stimulates–glucagon, TSH, epinephrine. G(i) inhibits.
What does cAMP do?
Activates cAMP dependent protein kinase A.
What does cAMP dependent protein kinase A do?
Phosphorylates target proteins at Ser and Thr residues.
What is the off mechanism for cAMP?
cAMP is hydrolyzed by phosphodiesterase. Proteins are dephosphorylated by protein phosphatases.
What are the steps in sugar metabolism regulation?
1) Glucagon binds to GPCR
2) G(s) is activated
3) GPCR activates G(s)
4) G(s) activates adenylate cyclase
5) Adenylate cyclase increases cAMP
6) cAMP increases PKA activity
7) PKA phosphorylates phosphorylase kinase, which activates glycogen phosphorylase
8) PKA translocates to nucleus and phosphorylates the cAMP response element binding protein, called CREB–a transcription factor
What is the off mechanism for sugar metabolism?
G(s) inactivates itself, exchanges bound GTP for GDP.
cAMP is removed by PDE (phosphodiesterase).
What is the phosphatidylinositol pathway? What hormones does it act with?
Hormones: acetylcholine,
vasopressin, epinephrine.
G protein activates phospholipase C (PLC). This generates two second messengers:
1) diacylglycerol (DAG)
2) inositol triphosphate (IP3)
DAG activates protein kinase C (PKC).
IP3 causes release of Ca2+ that activates other protein kinases.
What are receptor tyrosine kinases? What hormones do they act with?
Hormones: insulin, epidermal growth
factor (EGF), platelet-derived growth
factor (PDGF), insulin-like growth
factor I (IGF-I)
RTK undergoes autophosphorylation when stimulated (aka when a hormone binds)–this occurs at specific Tyr residues. Also often requires ATP hydrolysis.
This triggers a phosphorylation cascade.
Describe the structure and activity of the insulin receptor. What type of receptor is it?
Receptor tyrosine kinase.
Forms alpha-2-beta-2 tetramer in membrane. Alpha subunits are insulin binding site. Beta subunits have RTK activity.
What happens when insulin binds to the receptor?
Insulin binds to the insulin receptor in the insulin responsive
tissues (e.g. muscle and adipose tissues) to
increase glucose uptake and metabolism by
triggering translocation of Glut-4 to plasma membrane
and influx of glucose, glycogen synthesis,
glycolysis and fatty acid synthesis
