Chapter 15 Part 1 Flashcards
Cell Signalling and Transduction
extracellular response sequence (eight principles)
1) synthesis of signalling molecule
2) release of the molecule by exocytosis
3) movement of molecules to target cell
4) the molecules act as ligands to bind to the protein receptor on the target cell
5) binding causes a conformational change in the receptor
6) that initiates intracellular pathways
7) the receptor then gets deactivated and the ligand is removed
List the 4 types of intracellular signalling
- endocrine
- paracrine
- autocrine
- justacrine
What is endocrine signalling
the message molecules go through the bloodstream to be delivered to the target cell (ex. insulin)
What is paracrine signalling?
the message molecules only travel a short distance through extracellular space to target cell
what is autocrine signalling?
the cell itself releases messages molecules that go to receptors of the surface of the cell
What is juxtacrine signalling?
aka contact depending signalling. the target and secretary cells are adjacent to each other and most be physically in contact with each other. The secretory protein releases plasma membrane attached proteins to the target cell
What are the 3 types of cell surface receptors
- enzymes linked
- g protein coupled
- ion channel linked
What is an intercellular receptor?
it is when the small hydrophobic molecules diffuse through the membranes and bind to the receptor protein in the nucleus or the cytoplasm
What is a first messenger molecule?
it is an extracellular ligand that will bind to the transmembrane to activate a second messenger response or turns it’s domain into a recruiting centre for cellular signalling proteins
What are the 2 different signalling pathways?
- initiate a second messenger response
- turn its domain to a recruiting centre for cellular signalling proteins
What is a second messenger molecule?
in one type of signalling pathway, the transmembrane receptor will signal an enzyme called an effector to generate a second messenger molecule
What can a second messenger molecule do?
- it can activate or deactivate a protein by modifying the protein
- it diffuse through the cytosol or get imbedded int he lipid bilayer
Which amino group residues are usually phosphorylated?
- serine
- threonine
- tyrosine (sometimes)
What is amplification
when one small ligand can illicit a large response in a cell (usually each step the amount of molecules gets multiplied)
What are the types of receptors?
- G protein coupled receptor
- ligand gated coupled receptor
- receptor kinase
- nuclear kinase
What does it mean when protein domain dock?
allows domains of the receptor and other domains to interact
What does kinase mean?
phosphorylate
What does phosphorylate mean?
dephorsphorylate
What regulates phosphorylation and dephospohorylation?
first messenger ligands
What are GTPases
an enzyme that hydrolyzes GTP to GDP changing the protein from active to inactive
- it usually has help from some GTPase regulatory proteins like GAPs, RGSs, GDI & GEF
what is GAP?
it is a GTPase activating protein
- changes GTP to GDP by increasing the hydrolyzing power thus shorten the protein mediated response
What is RGS
regulators of G protein signalling
- similar to GAP but done in a different location
- can deactivate a g protien
What is GDI?
its a guanine nucleotide dissociation inhibitor
- doesn’t allow the GdP to dissociate so protein remains in an inactive state
What is GEF
guanine nucleotide exchange factor
- factor needed to change form inactive to active by stimulating dissociation of g proteins
(inactive to active: GDP to GTP and active to inactive: GTP to GDP)
Examples of GTPases
- Rho
- Ran
What is a G protein and what are the names of the subunits?
is a protein composed of 3 subunits (Alpha, beta, and gamma) that is covalently bonded to membrane
what are the other names for G protein?
- large G protein
- heterotrimeric G protein
What is the structure of a GPCR
it is a receptor that has 7 transmembrane helices and a ligand binding spot and is coupled with a G protein
What is special about the alpha subunit?
it is a GTPase
How does signal transduction get started with a GPCR?
it is called activation
- the ligand will bind to the extracellular part of the domain and change the confirmation of the intracellular domain
- that increases the receptor affinity to the G protein
What is GRK and what does it do?
it is the G protein coupled receptor kinase phosphorylation site
- its located in the cytosol and its the site for downregulation
What is PKA?
Protein kinase A phosphorlaytion site used for down regulation
What are the movement of proteins during signal transduction in GPCR
1) ligand binds inducing a conformational change in the receptor
2) This change increases the affinity to a G protien
3) Binding causes change in Ga triggering dissociation of GDP
4) GTP binds and the Ga dissociates
5) Ga binds to the effector activating it
6) GTP is hydrolyzes causing dissocation with the effector and rebinds to the other subunits
What is desensitization?
the activated GCPR will make the GRK phosphorylate itself allowing arrestin to bind and desensitize the GCPR
What is inactivation?
termination of the response and its usually caused by desensitization
What is arrestin and what does it do?
they are proteins that compete with G protein’s spot on the receptor causing the receptors to be inactivated even if a ligand has binded
how does a cell get resensitized?
the receptor is recycled and returned o the surface of the cell
what is a effector?
it is the enzymes that catalyze the formation of then second messengers
What is adenyl cyclase and what does it do?
it is a effector that makes cyclic AMP (cAMP)
How is cAMP generated?
by adenylyl cyclase as a second messenger response
How is cAMP related to PKA
cAMP activates protein kinase A
what is AKAP?
it is a kinase anchoring protein that can be cell/tissue specific and it can confine PKA to
- microtubules
- ion channels
- mitochondria
- nucleus
