CBG.10 Flashcards
What are the 4 main types of signalling pathways?
Autocrine
Paracrine
Endocrine
Juxtacrine
explain how autocrine pathway works, giving an example?
autocrine is self stimulation, so it is short distance. for example interleukin 2 from a stimulated T cell causes the T cell to proliferate monoclonally
What is the paracrine pathway?
paracrine is signalling between local cells, for example neuronal signalling, and many growth factors
explain the endocrine pathway
the endocrine pathway is signalling between distant cells, for example insulin signalling via the blood in mammals, or gibberellin via xylem in plants
explain the juxtacrine pathway
juxtacrine pathway is direct contact between cells, often via membrane bound ligands, for example Th cell stimulation of B cells, also gap junctions and plasmodesmata are other good examples.
what three different effects can acetyl choline have on different cells?
heart muscle cells- decreases the contraction rate of the heart muscle
salivary glands - causes secretion of enzymes
skeletal muscle cells - causes contractions
what are the five main classes of cell signalling recptors?
- nuclear receptors
- G protein coupled receptors
- enxyme coupled receptors
- ligand gated ion channels
- adhesion receptors
give an example of a ligand gated ion channel
Nicotinic ACh recptor is a ligand gated Na+ channel
where can you find Nicotininc ACh receptor Na+ channels?
musculoskeltal junctions
CNS synapses
what are the agonists and antagonists for the Nicotininc ACh receptor Na+ channel?
Nicotine is the agonist - it opens the channels
Curare is the antagnoist - it blocks the channels, i.e paralysis
what are nuclear receptors?
They are ligand modulated gene regulatory proteins, which bind hydrophobic signalling molecules
Give three examples of hydrophobic signalling molecules for nuclear recptors
Oestrogen - a sex steroid hormone
Retinoic acid - vitamin A acid, also a morphogen
Thyroxine - human growth hormone
once nuclear receptors have bound to their ligand hormones what are they able to do?
Nuclear receptors are then able to bind to DNA
How are steroid receptors antagonists used in medicine?
They are used for chemotherapy for treatment of breast cancer. Most breast cancer cells require oestrogen to divide, the steroid recptor antogonist tamoxifen blocks oestrogen receptors, therefore stopping cell division and proliferation.
what is tamoxifen used for in drug treatment?
it is used to treat breast cancer as it is able to block oestrogen recptors. Most breast cancer cells require oestrogen to divide.
when a G protein is bound to GTP is it in its active or weak form?
active
when a G protein is bound to GDP is it in its active or weak form?
weak
what are G proteins?
weak GTPases, which are time delayed biological switches
what does GAP stand for?
GTPase activating protein
what is the function of GAP?
it increases the GTPase activity of a G protein
what does GEF stand for?
guanine nucleotide exchange factor
what does GPCR stand for?
G-protein coupled receptors
what is the function of GPCRs?
they act as ligand modulated GEFs, for example for adrenaline
what are GPCRs?
they are proteins which are G-coupled receptors,
which have 7 ubiquitous transmebrane receptors
How do GPCR amplify their signal?
they act through secondary messengers such as cAMP and IP3/DAG
What happens when adrenaline binds to a G coupled receptor?
It results in a chain of events - firstly it causes the ADP bound to the alpha subunit of the G coupled receptor to convert to ATP
The alpha ATP complex dissasosiates from the GPCR and binds to adenylate cyclase
Adenylate cyclase converts ATP to cAMP
cAMP binds to AK - PKA complex
PKA dissasosiates from the complex
PKA phosphorylates CREB, a TF
CREB passes through a nuclear pore into the nucelolus and induce transcription
what is the function of adenylate cyclase?
converts ATP to cAMP
what are three characteristics of the cAMP signalling system?
Amplification
Sharp response
Short duration
how is cAMP removed from the cell?
cAMP allows PKA release, PKA activates phosphodiesterase which rapidly removes cAMP
how many cAMP are needed to release PKA?
4
what is amplification?
small signal leading to a much larger signalling cascade
can protein kinases act as a biological switch?
yes. phosphorylation by protein kinases acts as a biological switch, activating proteins, e.g tyrosine or serine/threonine
Receptor tyrosine kinases
receptor tyrosine kinases are single pass enzyme coupled transmebrane receptors
what are the characteristics of the extracellular receptor domain of RTK
cysteine rich or globulin like
give 2 examples of ligands which act on RTK
epidermal growth factor
insulin
once a ligand has bound to a RTK what happens next?
the RTK dimerise and then acts through phosphorylation cascades
which transcription factor is activated/phosphorylated as a result of epidermal growth factor binding to EGF RTK?
Myc
what does Myc bind to?
enhancer box sequence
what does a mutation in Ras likely result in?
cancer
what is the cause of neurofibromatosis?
Ras-GAP mutation
which membrane bound receptor is involved in most growth factor cascades?
Receptor tyrosine kinases
