Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/54

Click to flip

54 Cards in this Set

  • Front
  • Back

Which G protein subunits are anchored in the cytoplasmic leaflet?

G-alpha and G-gamma

What G protein subunit interacts with the effector molecule?

G-alpha

What are the components of a GPCR signaling cascade?

1. ligand


2. GPCR


3. trimeric G-protein


4. effector (ie adenylyl cyclase)


5. second messenger (cAMP)

What causes the G-alpha subunit to disassociate from the effector molecule and reassociate with the G-beta and G-gamma subunits?

Hydrolysis of the bound GTP to GDP

What is the most common effector enzyme and second messenger in GPCR signaling?


What downstream pathway does this activate?

Adenylyl cyclase


cAMP


PKA

What effector, downstream pathway, and function is associated with cGMP?

Gyanylyl cyclase


PKG


Optical rod cells

What are the second messengers generated by Phospholipase C? What does each one do?

DAG -> activates PKC


IP3 -> causes release of Ca++ from ER

What type of receptors bind a stimulatory G-alpha protein w/ cAMP as the second messenger?

B-Adrenergic (epinephrine R)


Receptors for glucagon, serotonin, vasopressin

What type of receptors bind an inhibitory G-alpha protein w/ cAMP as the second messenger?

a2-Adrenergic receptor


Muscarinic ACh receptor

What are the subunits of PKA? What do they bind/where do they go?

2 regulatory: bind cAMP


2 catalytic: enter nucleus and phosphorylate CREB

What proteins can PKA phosphorylate?

CREB & MAPK

What is the signaling pathway from PKA through changes in gene expression?

PKA -> CREB-P -> creDNA + CREB-P + CBP/p300

Where is GPCR/cAMP signaling commonly used to change metabolism? What are the ligands/hormones responsible?

Adipose, liver, skeletal muscle


Glucagon & epinephrine

What does PKA activation do in cardiac cells?

Increases heart rate

What does PKA activation do in liver and skeletal muscles?

Mediates glycogen hydrolysis to produce glucose, and TG hydrolysis to produce FAs

What does cholera toxin do to GPCR signaling? What are the effects? What tissue?

Modifies a G-alpha stimulatory subunit, which causes the subunit and adenylyl cyclase to remain active -> high cAMP -> constant PKA activity -> activation of CFTR Cl- channels


-Results in Cl- anions and water to flow into intestinal lumen...diarrhea


What does Whooping Cough bacteria (bordatella pertussis) do to GPCR signaling? What are the effects? What tissue?

Modifies a G-alpha inhibitory subunit, which prevents GDP release -> inhibition is inhibited. Therefore high cAMP -> activated PKA -> activation of CFTR Cl- channel -> fluid loss and increased mucous secretion into lungs


-Alveolar epithelial cells

What is the mechanism of heart failure?

1. Elevated levels of catecholamines (epinephrine)


2. Chronic stim of B-AR/Adenylyl cyclase/PKA


3. Problems with re-sequestering Ca++ will decrease the amount that can be released -> decreases in Ca++ pools in ER will weaken subsequent contractions

What is the series of events in normal cardiac muscle contraction?

Epinephrine binds B-adrenergic R -> activates GPCR -> adenylyl cyclase -> cAMP -> PKA -> phosphorylates Ryanodine receptor (in SR) and T-tubule -> Ca++ influx -> muscle contraction

What can be used to treat hypertension, cardiac arrhythmias, heart attacks, and heart failure?

Propranolol ie B-blockers, which block B-AR signaling/ epinephrine signaling

_____ can become _____ which can be cleaved by PLC into DAG and IP3

PI (phosphatidylinositol)


PIP2

How is PKC activated?

1. PLC causes cleavage of PIP2 into DAG and IP3


2. IP3 causes release of sequestered ER Ca++ stores


3. Ca++ helps bring PKC to the plasma membrane


4. DAG at the plasma mem activates PKC


5. PKC can now phosphorylate target proteins

Smooth muscle relaxation is an example of what kind of signaling? Which tissues are involved?

Paracrine


Endothelial & smooth muscle cells

What is the mechanism / pathway of smooth muscle relaxation in the endothelial cells?

ACh -> GPCR -> PLC/IP3 -> Ca++ complexes with calmodulin -> activates NO synthase -> produces NO, which diffuses to smooth muscle cells

What is the mechanism / pathway of smooth muscle relaxation in the smooth muscle cells?

NO -> GPCR -> Guanylyl cyclase/cGMP -> PKG -> relaxation of smooth muscle

What are the 3 types of single pass receptors?

- Cytokine receptors


- Receptor tyrosine kinases (RTKs)


- TGFBeta receptors

Which type of single pass receptor has an extrinsic kinase?

Cytokine receptor

What happens to single pass receptors upon ligand binding?

DIMERIZE!

What is the extrinsic kinase of cytokine receptors?

JAK

How is JAK activated? What domain?

By dimerization of the cytokine receptor, which autophosphorylates on tyrosine residues on the JAK Lip domain

What JAK do once activated?

Phosphorylates tyrosine residues on the intracellular domain of the receptor, which will serve as a docking site

Phosphotyrosine residues can serve as docking sites for which kind of domains?

SH2, PTB


Also SH3

What domain allows STAT to dock with cytokine receptors?

SH2 + phosphotyrosine (on receptor)

How does STAT get into nucleus? (Full pathway)

Cytokine R -> dimerization & activation of JAK -> phosphorylation of R -> docking of STAT -> JAK phosphorylates STAT -> STAT dimerizes through SH2/phosphotyrosine domains -> dimerized STAT goes to nucleus

Cytokine (JAK/STAT) signaling is involved in which processes? (3)

1. interferon signaling


2. lactation


3. hematopoietic cell differentiation

What signal stimulates erythropoeisis through a cytokine-JAK/STAT pathway? Where is it produced?

Erythropoietin


Kidney

What type of single pass receptors are associated with monomeric G proteins?

RTKs

What proteins mediate the activation of G-proteins (GDP -> GTP)?

GEF

What proteins mediate the inactivation of G-proteins (hydrolysis of GTP -> GDP)?

GAP

What 2 proteins dock on the phosphotyrosine residues of RTKs?

SOS and GRB2

What is the pathway/mechanism of MAPK activation via RTKs?

RTK dimerizes -> docking of SOS -> SOS binds Ras -> Ras activated (GDP->GTP) -> Ras disassociates from SOS -> Ras activates MAPK

What is the GEF for monomeric G protein Ras?

SOS

What mutations are often associated with cancer?

Hyperactive or constantly active Ras

What is the pathway of MAPK activation, starting with Ras?

Ras -> Raf (MAPKKK) -> Mek (MAPKK) -> Erk (MAPK)


all are kinases

What are some examples of RTK families?

EGFR (epidermal growth factor R)


VEGFR (vascular endothelial growth factor R)


Insulin R

What is a common example of a receptor mutated in breast cancer? What type of receptor is this? What pathway does it signal through?

HER1-4


RTK


Ras-MAPK

What is the pathway of TGFB single pass receptor signaling?

TGFB -> binds RIII or RII receptor (already phosphorylated) -> recruits & phosphorylates RI -> phosphorylates Smad3 -> 2 Smad3 + 1 Smad4 + importin go to nucleus

What protein helps Smad3 and Smad4 get to the nucleus?

Importin

What are the effects of TGFB signaling? (3)

-Secretion of extracellular matrix proteins


-Secretion of proteins that inhibit serum proteases


-Signals anti-growth properties

What is a serum protease inhibitor activated by TGFB signaling?

PAI1

What are the 2 proteins that mediate TGFB antigrowth properties? What are their specific roles?

p15: causes cell cycle arrest


PAI1: suppresses migration into tissues

What is often deleted in pancreatic cancer?

Smad4

What type of signaling, when absent, would allow uncontrolled growth of cancers?

TGFB

How is MS treated? What pathway does this take advantage of? Increases & decreases what?

Interferon therapy - through cytokine JAK/STAT signaling


Increases anti-inflammatory cytokines, inhibits inflammatory cytokines