100% satisfaction guarantee Immediately available after payment Both online and in PDF No strings attached
logo-home
Summary Cellular Signal Transduction (CST) $3.75
Add to cart

Summary

Summary Cellular Signal Transduction (CST)

5 reviews
 308 views  21 purchases
  • Course
  • Institution

Summary of the course Cellular Signal Transduction (CST) from the Bio-Pharmaceutical Sciences (BFW) minor (Computational Approaches to) Disease, Signaling and Drug Targets (DSDT).

Preview 4 out of 45  pages

  • January 29, 2019
  • 45
  • 2017/2018
  • Summary

5  reviews

review-writer-avatar

By: robertdemooij • 1 year ago

review-writer-avatar

By: kaursinghgurjit • 2 year ago

review-writer-avatar

By: isabellevandijck • 2 year ago

review-writer-avatar

By: lottederidder1 • 2 year ago

review-writer-avatar

By: rezadn92 • 5 year ago

avatar-seller
College 1 – Introduction
See writen notes.

Via GAP junctons it is possible to signal without a receptor. Small molecule scan transport to other
cells. Tumour cells have disturbed GAP junctons.

NF-κβ functons as a shutling method. NF-κβ transport in and out the cells, contnuously. This is
important for the transcripton of a set of genes.

Scafold proteins bring diferent signalling proteins together, so the proteins can wor together.


College 2 – GPCR signalling
The human genome consists of ~ 30.000 protein-coding genes. The druggable genome consists of ~
3.000 targets.

Cellular locatons of targets
 Cell-surface receptors
 Intercellular receptors

 All cells receive and respond to signals from their surroundings, li e from another cell (direct)
or from signalling molecules (indirect).
 Signalling molecules are secreted by one cell and bind to receptors expressed on other cells,
which ofen results in series of intracellular reactons.
 Many intracellular signalling proteins functon as switches that are actvated by
phosphorylaton or GTP binding.
 Proteins communicate by an actve and inactve state.

Current drug targets:
~ 800 GPCRs (~ 500 considered drug targets)
~ 25% of current drug target GPCRs

GPCRs signal from the outside of the cell all the way to the nucleus.

Examples of GPCR drugs:
 Beta bloc ers
 Drugs for migraine

 Tastng of food and smelling perfume goes via GPCRs, but these are not interestng for drug
targetng.

The phylogenetc tree of GPCRs is based on sequence homology and the classifcaton of GPCRs is as
follows:
 Class A: Rhodopsin-li e
 Class B: Secretn-li e
 Class C: Glutamate-li e
 Adhesion-li e and Frizzled receptors
 ‘GRAFS’




1

,GPCRs have 7 helices which go through the cell membrane. These helices form a barrel. Within these
receptors there is a orthostatc and allosteric ligand.  Ligand binding to the allosteric or orthostatc
binding site van give the same efect, but could be diferent. Dependent on the allosteric binding site.

The class B GPCRs have a long N-terminal, which consists the orthostatc binding site. The N-terminal
is rigid and fxed.

Receptors have several chemical messengers:
 Neurotransmiters
o Chemical released from nerve endings which travel across a nerve synapse to bind
with receptors on target cells, such as muscle cells or another nerve.
o Usually short lived and responsible for messages between individual cells.
 Hormones
o Chemicals released from cells or glands and which travel some distance (mostly via
blood) to bind with receptors on target cells throughout the body.
o Hormones are used to communicate between (distant) organs and tssues. Therefore
they are more long lived.
 Synthetc compounds (i.e. drugs)

Chemical messengers ‘switch on’ receptors without undergoing a reacton (unli e substrates for
enzymes).

Variety of natural ligands
 Light
 Catons
 Small compounds
 Peptdes
 Proteins

GPCR signalling: The ligand binds to the receptor, which leads to an intracellular response (ofen) via
G protein. A ligand has a certain afnity to a receptor, which determines the degree of binding.

2

,Equilibrium state of bound and unbound ligand determines the afnity. The more bound ligand, the
higher the afnity.
The ligand has binding groups and the receptor has binding regions in its binding site. The binding
groups and binding regions are bound to each other with intermolecular bonds. As said, this actvates
the G protein. Via second messengers the gene regulaton is actvated and eventually, this gives a
cellular efect.




There are various types of G proteins:
 Each G protein recognizes a partcular set of GPCRs
 Each GPCR can recognize one or more G proteins
All G proteins have a similar structure and operate similarly. They have three subunits: alpha, beta
and gamma.
 Gα-GDP is bound to a ‘silent’ receptor
 Actvated receptor results in GDPGGTP exchange on G α
 Gα is a GTPase  regulatesGterminates G protein signalling
Small monomeric GTPases (e.g. Ras and Rho) are another class of signal proteins.

The G-protein is also a ligand of the GPCR. The GDP bound state of the G-protein has a higher afnity
for the receptor then the GTP bound state.

G protein (de-)actvaton cycle




The Gαs pathway  Gαs protein-mediated actvaton of adenylyl cyclase causes formaton of the 2 nd
messenger cAMP. The cAMP-mediated actvaton of PKA causes actvaton of transcripton factors. A
rise in cAMP can alter gene transcripton.


3

, The Gαi pathway only wor s when the receptor is actve.
Consttutve means that the receptor is actve without the presence
of the endogenous ligand.




Note: inhibiton of bac ground actvity due to constant levels of G i and Gs actvity  overall efect
depends on dominant G protein, which is decided by which receptors are (consttutvely) actvated.

Gαq pathway:
Gq protein-mediated actvaton of plasma membrane-bound enzyme PLCβ causes formaton of 2 nd
messengers DAG and IP3. DAG actvated protein inase C, while IP 3 causes release of Ca2+ from
intracellular stores.
Ca2+-mediated actvaton of CaM- inase
causes actvaton of transcripton factors. 
A rise of Ca2+ can alter gene transcripton.




By an overactve GPCR there is a desensitzaton mechanism.
 Prolonged binding of agonist leads to C-term receptor phosphorylaton by Serine-Threonine
inases
 This results in β-arrestn recruitment, which leads to receptor desensitzaton
There is also a sensitzaton mechanism when, for example, there is prolonged binding of antagonist.

4

The benefits of buying summaries with Stuvia:

Guaranteed quality through customer reviews

Guaranteed quality through customer reviews

Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.

Quick and easy check-out

Quick and easy check-out

You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.

Focus on what matters

Focus on what matters

Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!

Frequently asked questions

What do I get when I buy this document?

You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.

Satisfaction guarantee: how does it work?

Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.

Who am I buying these notes from?

Stuvia is a marketplace, so you are not buying this document from us, but from seller nickykruit. Stuvia facilitates payment to the seller.

Will I be stuck with a subscription?

No, you only buy these notes for $3.75. You're not tied to anything after your purchase.

Can Stuvia be trusted?

4.6 stars on Google & Trustpilot (+1000 reviews)

52510 documents were sold in the last 30 days

Founded in 2010, the go-to place to buy study notes for 14 years now

Start selling
$3.75  21x  sold
  • (5)
Add to cart
Added