9-11 Cell Signaling I Flashcards Preview

MCBG EXAM 3 FINAL > 9-11 Cell Signaling I > Flashcards

Flashcards in 9-11 Cell Signaling I Deck (36):

What are the 2 key components required for Cell signaling?

1. 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}



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
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



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!


PKA (Protein Kinase A) is also known as a ___ ___ Kinase because _____
2)What is the EXACT sequence PKA requires for its job?

PKA is also known as a Serine/Threonine Kinase because it only phosphorylates proteins (cytosolic or membrane) with serene or threonine amino acids sequences

2)protein has to have R-R-X-[Ser/Thr]-[HydrphbcAA]


When serine-threonine protein enzymes are phosphorylated by PKA how are these proteins DEACTIVATED?

Protein enzymes phosphoryltd on serine/Thr residues by PKA can be DEphorphoryltd by a PHOSPHATASE
-->terminates the signal


How are PKA and CREB related?

PKA can also regulate gene tx by directly traveling into nucleus pores and phosphorylating CREB tx factor in nucleus!


What does a Phosphorylated CREB do?

Phosphorylated CREB tx factor binds to specific DNA seq. element called CRE(cAMP response element) and then associates w/CBP[CREB-binding protein] gene regulatory protein which stimulates target gene tx.


Compare the "timing" between cAMP signaling in the cytoplasm to the effects on gene tx within the nucleus?

cytosolic cAMP signaling IS FAST BUT
effects on gene tx within the nucleus from CREB and CBP takes hours!!!!


Explain G-protein coupled receptor desentisization

G-coupled rceptors are desensitized when GRK kinases phosphorylate the its cytosolic tails/loops. The phosphate is then recognized by ARRESTIN which binds & prevents coupled rceptors from interacting w/ Gprotein


What happens when Arrestin binds to a phosphorylated G-protein coupled receptor? [2]

1. Prevents G-protein interaction and Directs receptor to clathrin-coat endocytosis for
*sequestering, *dephosphorylation, *return to PM or *ubiquitnation/lysosome degradation=receptor down-regulation

2.prevents receptor from interacting w/G-protein and bound Arrestin itself can activate additional signal transduction pathways


Recite the LONG multi-step process of how Cholera causes Diarrhea? [6]

1. Cholera toxin enzyme places ADP-ribose from NAD+ on Arg-201 of [Gs]alpha subunit=ADP ribosylation
2. GTPase activity from the [Gs]alpha subunit is now inactivated now so it CAN NOT cleave off its active GTP

3. continuous active GTP on [Gs]alpha activates adenylyl cyclase over and over-->INC cAMP in intestinal epithelial cells

4. HIGH cAMP activates PKA a lot which phorphorylates CFTR chloride ion channel a lot
5. Cl- ion is secreted continuously and Na+ absorption is stopped which makes water jump into the GI lumen.
6. Diarrhea and Dehydration occurs as result of Water leaving body


How does the [Gi] protein and its coupled receptor work?

After its coupled receptor stimulates it to exchange the GDP for GTP active [Gi] protein-GTP INHIBITS ADENYLYL CYCLASE instead of activating it! -->DEC cAMP


What does [G]beta-gamma subunit dimer do?

After being activated in its GTP bound form from its coupled receptor this protein can
**activate certain K+ channels**



Similar to [p21/waf1/CKI] in function but instead does NOT need p53 for Activation---->
can inhibit [G1/S Cdk] from phosphorylating Rb and does this INDEPENDENTLY!


Tumor suppressor genes act in a ___[dominant/recessive] manner in contributing to cancer prevention

2)What does this ultimately mean for tumor development?

Most Tumor suppressor genes are RECESSIVE in nature and require 2 recessive alleles to work

2)With tumor suppressor genes you HAVE TO LOSE BOTH ALLELES in order to have a tumor develop