Lecture 22 - Cell communication and cell signaling II

Many G protein activate membrane-bound _____ that produce small messenger molecules

enzyme

What are the secondary messengers of GPCR pathways

• cAMP

• IP3/Calcium

What does cAMP stand for

cyclic adenosine monophosphate

What was the “original messenger” that was discovered

cAMP

What promotes the formation of cAMP

adenylyl cyclase (followed by the binding of ligands)

can you list all 7 steps of the GCPR signaling pathway?

(yes)

The cAMP pathway is considered a … response

fight or flight

cAMP is inactivated through …

hydrolysis to AMP

What enzyme catalyzes the hydrolysis of cAMP to AMP

PDE/ phosphodiesterase

What is the effect of caffeine in cAMP pathway

inhibits PDE

• cAMP levels remain higher

• sustained activation of PKA

What is the activation of PKA do

• increases glucose availability for increasing metabolism

• enhances neurotransmitter release

Cytosolic concentration of Ca is very __

low

The cytosolic Ca concentration is about _____ time lower than in the extracellular space

10,000

The ___ stores intracellular Calcium

ER

GPCR pathways can also generate _____ _____ that carries a signal to adjacent cells

dissolved gas

Most hydrophilic secondary messengers such as cAMP, IP3, and calcium cannot …

pass through the membrane and function only within the cell that produces them

Purpose of gas messengers

can pass through the membrane and carry signal to nearby cells

What is the downstream effect of the binding of acetylcholine

ACh binds to GPCRs —> production of IP3 and calcium

Ca activates ____ ____ synthesis from arginine

nitric oxide (NO)

When NO diffuses into smooth muscle cells in the adjacent vessel wall, the blood vessels _____

dialate

2 components of enzyme-coupled receptors

transmembrane proteins with ligand-binding domains (on cytosolic surface)

Enzyme coupled receptors act as ____ _____ at ___ ______

local mediators; low concentration

Dimerization

binding of an extracellular signal causes two receptor molecules to dimerize

What is the largest class of enzyme-coupled receptors

receptor tyrosine kinases (RTKs)

What do RTKs respond to (4)

• mitogens

• EGFRs

• INSRs

• VEGF

Each phosphorylated tyrosine acts as a _____ ____ for specific signaling proteins → relaying the signal to the cell interior

docking site

Most RTKs activate the protein

Ras

What is Ras

monomeric GTPase

What is a mitogen

signals that stimulate mitosis

Activated Gas activates ____

MAP3K (MAP kinase kinase kinase)

__ of human cancers contain Ras mutation

30

(T or F) Ras is considered a proto-oncogene

true

Example of Ras pathway

EGF pathway

Monoclonal antibody-based drugs that block EGFR will ___ effective in colon cancer patients with Ras mutation

not be

Some small, hydrophobic ____ _____ bind to intracellular receptors that act as transcription regulators

steroid hormones

Example of steroid hormones (3)

cortisol, estradiol, and testosterone

intracellular receptors can also be found on the _____

nucleus

Which 2 intracellular pathways crosstalk with eachother

GCPRs and RTKs

Which molecules are used to crosstalk between the GCPR and RTK (3)

IP3, phospholipase C, and calcium

Crosstalk between intracellular pathways is mediated by ____ _____

protein kinase

Why are there so many signal transduction pathway?

Allows cell to respond to a wide variety of extracellular signals

the amplification process can increase a signal by ___ to ___fold

10^6 to 10^9

What are there so many steps in each signal transduction pathway

• multiple points for crosstalk (integrate)

• signal diversification (distribution)

• feedback regulation (modulate)