Receptors and Diseases Flashcards
Why are receptors required?
To respond to environment spatial patterning apoptosis differentiation proliferation
How can receptors be classified?
Cell specific: synaptic or contact dependant
Cell type specific: Endocrine or paracrine
What are the main types of receptors?
GPCR
Enzyme coupled
Adhesion
Pathogen recognition
How many types of GPCR are there?
800
What is Jansens metaphyseal chrondrodysplasia?
Overactivation of kidney PTHr GPCR
Raises cAMP
Lack of Ca/P regulation
dwarfism
What is Hashimoto’s disease?
Antagonistic antibodies on TSHR
Decrease cAMP
Hypothyroidism
Weight gain
What is Grave’s disease?
TSHR agonist antibodies
Hyperthyroidism
Weight loss
Which toxins target GPCRs?
Cholera overactivates Gαs by ADP-ribosylation
Pertussis inhibits Gαi by ADP-ribosylation
Both raise cAMP
What is McCune-Albright Syndrome?
Somatic non-receptor defects in GPCRs
Cafe-au-lait phenotype produced by variation in melonocyte stimulating hormone
How is Pseudohypoparathyroidism caused?
Monoalleic inheritance and epigenetic silencing of PHPI gene causing loss of PTHr Gαs function
What are the different types of adhesion receptors?
Ig superfamily cadherins integrins selectins proteoglycans
What types of interactions do adhesion receptors mediate?
Homo/heterotypic
Cell-cell and cell-ECM
What type of adhesion receptor interactions are highest affinity?
homotypic
What interactions do integrins have?
αβ dimers bind RGD motifs in high affinity clusters
What type of interactions do selections mediate?
transient, low affinity binding of sialyl lewis sugars
Which organisms use adhesion receptors?
multicellular organisms for spatial patterning in embryonic development
What organisms have microbial receptors?
metazoans
What are the microbial receptors?
Surface Pattern Recognition receptors are toll like and carbohydrate binding lectins
What do microbial receptors do?
Bind PAMPS to stimulate cytokines and immune response
What affect do microbial SNPs have?
Increases susceptibility to microorganisms such as canidida
How are microbial receptors hijacked by pathogens?
HIV uses CD4 to enter cell
Listeria uses integrins for phagocytosis to release toxin into cell
What cellular responses do RTKs have?
Phosphorylation cascades to control ion balance, metabolism, glucose uptake, gene expression
What signalling molecules do RTKs respond to?
Growth signals
Insulin
How can type 2 diabetes be caused?
Desensitisation of receptor by FFA/excess glucose,
tyrosine phosphatases,
Clathrin dependant endocytosis
Downregulation of IRS by S/T phosphorylation
PI3K antagonist hormones produced by adipose tissue
IRS polymorphisms
How is type 1 diabetes caused?
Autoimmune attack of pancreatic β cells producing insulin
What are the main targets of insulin RTKs?
IRS1 for mitogenic activity
IRS2 for Glut4 translocation
What cellular responses does insulin cause?
Protein and glycogen synthesis
Transcription
Exposure of Glut4 receptos
What is the structure of the Insulin receptor?
Permanent extracellular dimer of αβ-βα subunits connected by disulphide bonds
How common are RTK receptors?
1/3 of all cell receptors
How are RTKs activated?
Ligand binds causing conformational change
Internal homodimerisation and transautophosphorylation
Recruits small G proteins in MAPK Ser/Thr kinase cascade
How can RTK mutations cause cancer?
Point mutations or deletion produces ligand independance, lack of autoinhibition
What perecntage of cancers are caused by viruses?
25%
How common are Ras mutations?
90% of tumours have no GTPase
30% caused by single substitution
What cellular responses are induced by RTK-MAPK activation?
Transcription factors,
cytoskeleton
Protein kinases
How can RTK cancers be treated?
Inhibitors of MAPK cascade
Inhibition on receptor by antagonistic antibodies
