Developmental signalling Flashcards
what does GPCR stand for
G-protein couples receptor
structure of a G -protein
7 transmembrane that winds back and fourth
GPCR are heterotrimeric
therefore three diff subunits, a, B and Y
a when bound to GDP
inactive
a when bound to GTP
active
activity in G-protein resides in…
a subunit
what breaks GTP back down to GDP
GTPase
when a ligand attaches to GPCR ….
second messengers to become active
Process of how a GPCR activates second messengers
1) ligand attaches to receptor and causes a change in shape
2) G protein (a-unit) moves towards the receptor
3) change in shape of receptor causes change in shape of alpha unit
4) alpha unit releases GDP and GTP takes its place- therefore activated
5) alpha unit separates from beta and gamma units and attaches to the receptor
6) this alpha unit starts the facade reaction by activating second messengers
7) reaction stops when GTPase breaks down GTP back to GDP
what percentage of pharmaceuticals largest GPCR
40%
cAMP pathway
LH attaches to receptor on the outside of the cell. This causes the alpha unit to release GDP and gain GTP–> activated. The activated alpha unit goes into the cell and teaches to adenyl cycle which it activates. This causes a cascade effect and turns ATP into cAMP and 2Pi.
cAMP can be used by the cell in many diff ways
uses of cAMP
transcription factors
enzymes that convert glycogen to glucose
enzymes thta promote muscle contraction
PKA
stages of the cell cycle
m
G1
S
G2
when does DNA replication take place
s
when does mitosis occur
m
2 checkpoints
G2/M
G1/S
what protein helps mediate the cell cycle
cyclin–> discovered because it seemed to appear and disappear with the cycles of cell division.
cyclin
induces cell division when injected into non-dividing cells
example of cyclin with RB (retina plasma)
enzyme linked receptors gain their ligand (GF) and this sends a message to the nucleus. The nucleus releases cyclin D. CyclinD attaches to CDK in the cytoplasm and this causes the Rb/E2F complex to separate. As a complex E2F cannot enter the nucleus, therefor eat must be separated. E2F can now act as TF and cause the production of proteins like DNA polymerase needed for cell division.
why is it bad if you are born without the Rb gene
if one is not born with Rb gene, the E2F will instantly enter the nucleus and this will caws uncontrolled cell division.
adenyl cyclase
an enzyme which synthesises cAMP from ATP
cyclic AMP
a second messenger in many important processes, used for intracellular signal transduction
Protein kinase A
family of enzymes who’s activity is dependent on the levels of cAMP (cAMP dependent pathway)
second messengers
are small, rapidly diffusible signalling intermediates
AMP phosphodiesterase
enzymes which break phoshodiester bonds
when lots of active adenylyl cyclase
high conc of cAMP
when lists of AMP phosphodiesterase
low conc of cAMP
kinases
add phosphates to things e.g. phosphorylates TF which cause a conformation change, therefore activated and can now promote transcription at particular sites of DNA
steroids
derived from cholesterol
-lipid soluble, therefore can pass csm
where are receptors for steroids found
the cytoplasm e.g. testosterone two receptors wrap around steroid and this is called a dimer, which can now enter the nucleus
Cell signalling can be
long or short (paracrine) response to an environmental change or a response to another signal
types of receptors
steroid
g-protein coupled
ion channels
enzyme linked
examples of peptides
hCG, LH and insulin
example of steroid
testorsterone
enzyme linked receptor signal transduction
1) VEGF binds to kinases on CSM
2) kinases cause the phosphorylation of 6 tyrosine molecules
3) these tyrosine then phosphorylate the GrB2 + SOS complex
4) then SOS catalyses the reaction which activates Ras molecule (binds it to GTP)
5) Ras causes a map cascade of phosphorylation
6) effector e.g. TF is phosphorylated
7) effector is now active and may enter the cells nucleus and cause translation of certain genes
cell signal response can be
- change in protein activity: turn enzymes on/off or reorganise cytoskeletal proteins
- changes in production of proteins- turns genes for proteins on/pff
endocrine
made and secreted from one organ and travels in the blood to target cells e.g. insulin
paracrine
local signalling (VEGF)
direct contact
with other cells directly eg. if a cell feels its adjacent cell tearing away from it
synaptic signalling
NT in nervous system
Ligand gated ion channels
can bee inotropic (fast e.g. at synapse) or metabotropic (slow
what ligand used GPCRs
LH, FSH, adrenaline,vision control
metabotropic
indirectly linked to ion channels
what releases VEGF the most
growing rumours that need a better blood supply
tyrosine kinase receptors
cell surface receptors for many polypeptide growth factors e.g. VEGF
why do tumour cells secrete VEGF
due to tumours growing faster than their blood supply–> hypoxia (lack of oxygen) tigers the release of VEGF for angiogenesis
Linked with cancers
angiogenesis
the production of new blood vessels
monoclonal antibodies
antibodies are y shaped proteins produced by plasma cells to neutralise and identify pathogens
therefor monoclonal antibodies are antibodies that are prodded by identical immune cells, that are all clones of a unique parent ce;;
monovalent affinity
antibodies Y shape bind to the same epitome
Vasculogenesis
growth of vessels
what type of molecule is VEGF
a grown factor, which is a signalling protein that promotes angiogenesis
what does VEGF bind to
tyrosine kinases- enzyme linked
classes of g protein coupled receptors
G alpha S- increase the conc of cAMP
G alpha q - produces ca2+ and diacylglycerol which activates protein kinase c–> phosphorylates proteins
G alpha o/i- causes reduction in cAMP by inhibiting adenylyl cyclase
why does phospholipase (protein kinase) cause the release of Ca2+
Ca2+ is stored in the smooth endoplasmic reticulum –> binds to ligand of ion channel and allows ca2+ to flow out
how does testosterone regulate its own production
-ve feedback to hypothalamus to reduce amount of GnRH, therefore less FSH and LH, therefore less testosterone produced by leydig cells
which cells release testosterone
leydig cell
