Exam 3 - Cell/Mol Phys

Chapter 16, 18

Both GPCR and RTKs activate multiple

intracellular signaling pathways

Starting from GPCR stimulation, what can cAMP generation lead to in a cell?

Fast response

or

Slow (latent) response

In most cells, cAMP exerts its effects via activating

cyclic AMP-dependent protein kinase (PKA)

Kinase (1-2%) types

Tyrosine kinases

Serine/Threonine kinases (more common)

Proper termination of signaling is as important as

the mechanisms that turn it on

Example of a disease caused by permanently activated G-protein

Cholera

GPCR activation of Phospholipase

requires both Ca2+ and DAG

What is the most common phospholipid

Phosphatidylcholine

Many extracellular signals trigger an increase in

Cytosolic Ca2+

Cytosolic Ca2+ concentration

10^-7 M

Extracellular fluid concentration

10^-3 M

Calmodulin

An example of Ca2+ binding protein that modulate Ca2+ level

Found in all eukaryotic cells

1% of total protein mass

Multi purpose intracellular Ca2+ receptor

CaM-Kinase

Calmodulin dependent kinase

Nitric Oxide (NO) as vasodilator

Nitric Oxide (NO) is a gas produced by endothelial cells upon nervous signal

Diffuse in and out of the cell membrane quickly, therefore must be synthesized on site where it can only travel and act locally

NO synthase produces NO using

arginine

Relaxation of smooth muscle cells results in

vasodilation

Vision

cGMP involved in vision transduction responses

Transducin

Activation of photo receptor results in a FALL of cGMP

Transducin

The fastest G-protein mediated responses known in vertebrate

Photoreceptor cell signaling transduction under dark

Outer segment (light sensitive) - inactive rhodopsin, cation channels open

Inner segment - cell depolarized

Nuclear region

Synaptic region - high rate of transmitter release

Photoreceptor cell signaling transduction under light

Outer segment (light sensitive) - activated rhodopsin, cation channels closed

Inner segment - cell hyperpolarized

Nuclear region

Synaptic region - low rate of transmitter release

Under ____, the receptor potential is a ______, NOT depolarization!

Light, hyperpolarization

Other types of neurons that are found in retina

Ganglion cells

Horizontal cells

Amacrine cells

Processing visual information

Begins within the retina where rods and cones (photoreceptor cells) make synapses with bipolar cells (neurons)

When cells respond to an extracellular signal, they most often convert the information carried by this molecule from one form to another. What is this process called?

Signal transduction

Many of the extracellular signal molecules that regulate inflammation are released locally at the site of infection. What form of cell–cell signaling is being used?

Paracrine

Each receptor is generally activated by only ___ type of signal molecule

one

___ feedback regulation can generate an abrupt, all-or-none response in which the cell moves from ignoring a signal to responding to it very strongly

Postitive

What is true of the GTP binding proteins that act as molecular switches inside cells?

They are active when GTP is bound

Which is true of the GTP-binding proteins that participate in intracellular signaling?

Only trimeric GTP binding proteins relay messages from G-protein-coupled receptors

What is true of ion-channel-coupled receptors?

They transduce signals in a simple and direct manner

Why does nitric oxide (NO) act as a paracrine signal that affects only neighboring cells?

It is rapidly converted to nitrates and nitrites in the extracellular fluid

Signaling via GPCR ceases when which condition occurs?

The a subunit hydrolyzes its bound GTP

What response to GPCR stimulation would be most rapid

Activation of a G protein that regulates the opening of an ion channel

When activated phospholipase C cleaves an inositol phospholipid, what happens to the small signaling molecules the enzyme produces?

Inositol 1,4,5-trisphosphate (IP₃) is released into the cytosol, while diacylglycerol is retained in the membrane

What are small intracellular signaling molecules often called?

Second messengers

Because cyclic AMP diffuses quickly through the cytosol and a cyclic AMP phosphodiesterase rapidly converts cyclic AMP to AMP, what is the consequence?

The cytosolic concentration of cyclic AMP can change rapidly

What do the phosphorylated tyrosines on activated RTK’s do?

They serve as binding sites for a variety of intracellular signaling proteins

Ras is activated by a Ras-activating protein that does what?

causes Ras to exchange GDP for GTP

RTKs can activate the enzyme phosphoinositide 3-kinase, which phosphorylates inositol phospholipids. These phospholipids then do what?

serve as docking sites that recruit specific intracellular signaling proteins to the plasma membrane

PI 3-kinase acts by phosphorylating what molecule(s)?

inositol phospholipids

Ethylene is a hormone that promotes the ripening of fruit. What happens in the absence of ethylene?

The activated ethylene receptor promotes the degradation of a transcription regulator and the ethylene-responsive genes remain turned off

Ras can exist in two different conformations or states, inactive and active. Which of the following correctly describe(s) the stably active state of Ras?

Ras is bound to GTP

Switch 1 and switch 2 regions are in an active conformation

Specific amino acids, including Arg 789 in Ras-GAP and amino acids Gln 61 and Thr 35 in Ras, all play an important role in Ras function. Why are these amino acids important?

They help facilitate GTP hydrolysis by Ras

Which of these represents a mechanism used to terminate a signal transmitted by activated RTKs?

The RTKs are internalized and digested in lysosomes

First messenger that starts signal transduction in smooth muscle cell

Nitric Oxide

Second messenger to start signal transduction in smooth muscle cell

Cyclic guanosine monophosphate (cGMP)

Cellular response caused by the signal transduction in smooth muscle cell

Relaxation of smooth muscle cell

Why do the arrows go from small to bigger in the cell signaling pathway

To represent signal amplification, initial small signal triggers progressively larger responses down the line

Where is the receptor that starts the cell signaling pathway

Intracellular, because the nitric oxide crosses the cell membrane directly to activate guanylyl cyclase (GC)

Ginseng is expected to ___ the production of nitric oxide

increase

Why is Ginseng expected to increase the production of nitric oxide?

Nitric oxide acts upstream to initiate the pathway by activating guanylyl cyclase (GC) to produce cGMP, increasing nitric oxide availability would boost the downstream signals leading to smooth muscle relaxation

What is viagra’s effect on PDE5?

Inhibits, blocks activity of PDE5

Specific mechanism of action that viagra has on PDE5

PDE5 normally breaks down and deactivates cGMP into 5’-GMP. By inhibiting PDE5, Viagra prevents the degradation of cGMP, causing cGMP levels to remain high, which prolongs PKG activation and maintains smooth muscle relaxation

If neither viagra nor ginseng works for erectile disfunction, what other proteins may be “broken”

Guanylyl cyclase (GC)

CGMP-dependent protein kinase (PKG)

Myosin light chain phosphatase (MLC P’tase)

Calcium regulatory proteins

____ signaling controls nerve-cell production in the fruit fly

Notch

Steroid hormones

must be bound to special carrier proteins to be soluble in blood

• derived from cholesterol

• bind to intracellular receptors

• receptor bound hormone tend to act as gene regulatory proteins affecting gene expression

The steroid hormone cortisol

acts by activating a gene regulatory protein

can limit the proteolysis of a specific protein that can lead to a response

Activation of Signaling

Ethylene

Gas that releases as fruit ripens

Default pathway

Active kinase action leading to transcription regulator degradation

Activation of receptor

prevents the degradation of transcription regulator that allows specific gene transcription

Intracellular signaling proteins serve to

integrate incoming signals

of proteins is critical for normal protein functions and cell signaling

Post translational modification

Various ___ are activated during signal transduction

enzymes

The central governor of growth and proliferation

The cell cycle clock

Cell cycle checkpoints

Impose quality control to ensure that a cell has properly completed all the steps of one phase of the cell cycle before the next one

The key molecules that regulate timing of cell cycle is

Cyclin

Cyclin-dependent protein kinase (Cdk)

Maturation-promoting factor

CDK-cyclin complex

Activity was discovered by injecting Xenopus egg cytoplasm into Xenopus oocytes

The activity of some Cdks is regulated by cyclin

degradation

Cell cycle arrest

Delayed stage gives cell more time to fix the problem

complex “pulls the trigger” once the proteins assemble as pre replicative complex

S phase Cdk complex

activates the DNA helicase and promotes the replicate fork assembly

S-Cdk

The ___ of nuclear pore proteins and lamina helps trigger the disassembly of the nuclear envelope

phosphorylation

promote the production of the cyclins that stimulate cell divison

Mitogens

G1-Cdk complex

Cyclin D

What can cause overproliferation, leading to cancer?

Mutations

• Gain of oncogenes

• Loss of tumor supressor genes