9-11 Cell Signaling I Flashcards
What are the 2 key components required for Cell signaling?
- Signaling molecule (hormone, NTS)
2. Receptor Protein [Cell-surface vs. Intracellular]
Signaling Categories are defined by the _____.
2) What are the 5 Signaling Categories
1)Signaling Categories/Types are defined by the SOURCE OF WHERE SIGNALING MOLECULES COME FROM
2) A. Contact-Dependent
B. Paracrine [1 signal affects diff types of target cells]
C. Synaptic
D. Endocrine[hormone TRAVELS and then affects target]
E. Autocrine [signaling from cell A also binds to cell A]
Although Cells depend on _____ extracellular signals to function (Survive, grow, differentiate, etc.) . What does a cell need in order to respond to these signaling molecules?
Although Cells depend on MULTIPLE extracellular signals to function…Cells ONLY respond to signaling molecules ONLY if it has specific receptor for that signaling molecule!
Explain how hormone effects from 1 type can vary in different cells?
2)What is an example of this? [3]
effects from 1 hormone in Cell A can vary in Cell B depending on the type of receptors and how the cell is programmed to respond
2) acetylcholine contracts skeletal muscle {nicotinic rcptr}
but DEC contraction of Heart muscle rate/force {M2 rcptr}
and induces secretion in salivary glands{M3 rcptr}
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Why are Hydrophobic molecules at an advantage for intracellular signaling?
Some hydrophobic signaling molecules pass thru plasma and then nuclear membranes(passively or transport) and activate intracellular nuclear receptors!
What happens when hormone molecules bind to their intracellular nuclear receptors?
2)What’s an example of some of these hydrophobic molecules?
After hormones bind to nuclear receptor proteins, nuclear receptors undergo conformational chnge-> dimerize(in most cases)->inhibitory protein release and coactivator/corepressors attach to receptor which is bound to specific DNA seq. regulating gene tx
2) STEROIDS (cortisol, estradiol, testosterone, Vitmn D)
What is Primary(___) response and Secondary Response?
2)How do Primary-response proteins autoregulate themselves?
Primary(early) response=when cell responds to steroid binding to steroid nuclear receptors by “early acting” & activating primary response genes (usually tx factors).
Secondary response=When primary response proteins activate tx of other genes(delayed process) to produce secondary response proteins
2) Primary-response proteins can stimulate tx of other genes (secondary) OR turn off primary-response genes=feedback inhibition
Describe the structure of Nuclear receptors [4]
- Structurally related to each other
- contains:
1. DNA-binding domain
2. ligand-binding domain
3. Transcription-regulating domain
MOST signaling molecules act on the _____receptors!
B: What are the major classes of this receptor?
C: How do they function?
MOST signaling molecules act on the CELL-SURFACE RECEPTORS!
B: Ion-Passing channel / enzyme-associated / G-protein coupled [GCPR]
C: These are “transducers” of an outside signal across the Plasma membrane into the inside
Describe the CELL-SURFACE enzyme-associated receptors?
signal molecule in a form of a dimer binds to enzyme-coupled receptor–>induces activation of catalytic domain or activation of enzyme attached to that domain
Describe the structure of G-Protein Coupled Receptors [GPCR]
2)Where do hormones actually bind?
Big receptor protein w/7 transmembrane helices(spans membrane 7 times) and binds signaling molecules outside the cell while interacting w/G-proteins(alpha,+beta+ gamma combo units) inside the cell
2)With GPCR hormones bind to N-TERMINAL EXTRACELLULAR SIDE! (C-term is inside the cell)
Explain the orientation of the intracellular C-terminal
[G-protein] [4]
G-protein (bound to a 7 transmembrane coupled receptor) is trimeric and has alpha+beta+gamma subunit combo!
2) alpha and gamma subunits are tethered to the membrane with a lipid tail
3) gamma subunit is glued to the beta subunit for life!
4)INACTIVE form=GDP is bound. When GDP released and exchanged for GTP –>activates G-protein alpha subunit AND beta/gamma——–(leads to)–>activates target enzyme by alpha subunit
G-protein has to have a ____attached in order to be “active” and activate target enzymes/proteins. What is responsible for promoting this initiation?
G-protein has to have a attached in order to activate inner cell target enzymes/proteins. Signaling molecule from outside binds to the G-coupled receptor which then promotes G-protein to release its GDP and pick up a
GTP—>Activated G-protein!
1) How do you INACTIVE an active G-protein alpha/beta-gamma subunit?
2) What components can accelerate this type of inactivation?
1) when the alpha-subunit hydrolyzes its GDP«—GTP and releases a phosphate ion (GTPase activity) it becomes inactive
2) the Target Enzyme, ion channels or RGS[regulators of G-protein signaling] can accelerate INactivation of G-proteins
[T or F] activated alpha-subunits can both ACTIVATE OR DEACTIVATE Target Enzymes and Proteins
TRUE!
IN the [Gs] G-Protein Family what subunit mediates all the action?
2) What Family # is this and what function does it have?
[Gs]=alpha subunit mediates action!
2) Family 1–>activates adenylyl cyclase and Ca+ channels
IN the [Gi] G-Protein Family what subunit mediates all the action?
2) What Family # is this and what function does it have?
[Gi]= alpha subunit mediates action!
2) Family 2–>INHIBITS adenylyl cyclase
IN the [Gq] G-Protein Family what subunit mediates all the action?
2) What Family # is this and what function does it have?
[Gq] = alpha subunit mediates action!
2) Family 3–> activates phopholipase C-beta
Which G-Protein Family members utilize the Beta-Gamma subunits to mediate their actions?
[Go] G-protein of Family 2 uses activated Beta-Gamma subunits instead of alpha
Humans have ____possible alpha subunits, ______beta subunits and _____gamma subunits that can compose the trimeric G-protein
20 possible alpha subunits, 6 beta subunits and 11 gamma subunits that can compose a trimeric G-protein in humans
How are the Family categories of Trimeric G-proteins actually determined?
by the relatedness of the amino acid sequence in alpha subunits
adenylyl cyclase
2)What activates adenylyl cyclase to do its job?
enzyme that hydrolyzes ATP to form cAMP
2)activated when its [Gs] coupled receptor receives a signaling molecule and the [Gs]alpha subunit gains a GTP as a result. Gs]alpha]GTP–>activates adenyly cyclase
What happens to cAMP after ____ _____ creates it from ATP
After adenylyl cylase forms cAMP from ATP it is HYDROLYZED and Inactivated to 5’AMP by [cAMP phophodiesterase]
1) cAMP binds to the ____ ___ of inactive ____ which causes_________
2) What does PKA (Protein Kinase A) do?
cAMP binds to regulatory subunits of inactive PKA which causes its release and activation!
2)PKA goes off to phosphorylate (from ATP) specific serene or threonine amino acids in proteins altering their activity!
