Exam 4 Flashcards
What are the three steps of biosignaling and cell communication?
- Reception
- Transduction
- Response
What are the two important parameters of each pair of signaling molecule & receptor?
- Kd: dissociation complex
- Bmax: maximal binding capacity
What are the different types of effectors?
growth factors, hormones, neutrotrasmitters, ligands, signals
What are characteristics of binding proteins?
- specificity
- amplification
- modularity
- desensitization/adaptation
- integration
What is the concept of modularity?
each pathway contains multiple protein components that have multiple domains which can interact in multiple pathways; this provides flexibility in the regulation of these pathways
What is the concept of desensitization?
each signal is transient; transduction is triggered but only lasts for a few seconds; thereafter even with the signal present, there is not response; reduction of receptors at cell surface
What is the concept of integration?
each cell have multiple transduction pathways that leads to multiple cell responses; the response is dependent on all the signal combined
What kind of bond exists between a ligand and its receptor?
weak, reversible, noncovalent interactions: electrostatic, hydrogen-bonding, and Van der Waals’ interactions and the hydrophobic effect
What is the constant / value that reflects the affinity of binding?
Kd
What is the constant / value that reflects the amount of receptors on cell surface?
Bmax
What is an agonist?
a drug that mimics the natural signal; binds to the receptor to trigger transduction
What is an antagonist?
a drug that binds to the receptor but does not trigger a response
How many types of signaling mechanisms does multicellular organisms have and what are they?
There are six:
- G protein coupled receptor
- Receptor tyrosine kinase
- Receptor guanylyl cyclase
- Gated ion channel
- Adhesion receptor (integrin)
- Nuclear receptor
What are the different types of ion channels?
- ligand-gated channels
- voltage-gated channels
- mechanically gated channels
What are the three important second messengers in ion channels and what do they do?
- Cyclic AMP: opens channels in olfactory and gustatory cells
- IP3 - opens calcium channels in ER membrane
- cyclic GMP - keeps sodium channels open in rod outer segments
What do G proteins do in ion channels?
open potassium channels in response to activation by receptors for various ligands, including acetylcholine, serotonin, dopamine, somatostatin, and g-aminobutyrate
How is the insulin receptor different fromthe other receptor of tyrosine kinases?
it consists of an alpha and beta subunit; the alpha is responsible for binding of the subunit and the beta is responsible for kinase activity; also, it undergoes conformational chnage
Except for the insulin receptor, what is the first step for all the other tyrosine kinase receptors and what happens after that?
dimerization which leads to autophosphorylation which activates the kinase activity to phosphorylate downstream products
Does autophosphorylation happen in the cis or trans formation and why?
trans because they need to be facing each other to autophosphorylate each other
How does phosphorylation of tyrosine kinase lead to activation?
the unphosphorylated kinase residues occupy the active sites ; when those tyrosine residues are phosphorylated, it undergoes conformational change and moves away from the binding site and the sites are now exposed
T/F: Many SH2 proteins are adapter proteins.
True
What are the ways in which the SH2 domain can propagate the growth factor signal?
- recruiting binding partners to the membrane
- facilitating tyrosine phosphorylation
Explain insulin signaling via the PI-3K/ PKB pathway.
- insulin phosphorylates IRS-1
- which activates PI3K
- which converts PIP2 to PIP3
- which binds to PKB
- which phosphorylates GSK3 and inactivate it
- GSK3, when activated, shuts down GS (glycogen synthase)
How does phosphorylation of GSK3 inactivate it?
phosphorylation causes the serine residue to go conformational change and blocks the binding site
