Mech of Hormone 174 Flashcards
What are common features of ligands for nuclear receptors?
small
lipophilic
synthesized by enzymes from precursors or sourced exogenously (i.e. not encoded by genome)
How are nuclear receptors classified?
classified by ligand type
i.e. hormones, vitamins, metabolites
What is the hormone response element of nuclear receptors?
a region of DNA that is specific to a particular receptor
often close to the promotor of genes regulated by the particular receptor
How are nuclear receptors regulated?
can be regulated on the ligand level (availability, synthesis, secretion, activation, clearance) or on the receptor level (whether or not a cell expresses a receptor)
also related to coactivators and corepressors
What are the consequences of nuclear receptor activation?
regulates gene transcription
can either upregulate it or downregulate it
What type of receptor is dysfunctional in the following diseases: THRB resistance, complete androgen insensitivity syndrome, hereditary vitamin D resistance.
nuclear receptor disorders
thyroid hormone, androgens, and vitamin D all signal to nuclear receptors
What are the six major classes of membrane receptors?
What are the components (3) of receptor tyrosine kinases?
1) extracellular ligand binding domain
2) single transmembrane domain
3) intracellular tyrosine kinase catalytic domain
What structural changes occur to receptor tyrosine kinases after ligand binding?
they dimerize
sometimes they also autophosphorylate (ex. insulin)
What is the function of receptor serine/threonine kinases?
a dimerizing membrane receptor that phosphorylates serine and threonine
What is the general pathway of cytokine activated receptors?
a membrane receptor that is activated by cytokines and acts on associated tyrosine kinases (JAK/STAT pathway)
What are major cytokine activated receptors?
growth hormone (needed for growth)
prolactin (needed for reproduction/lactation)
leptin (suppresses appetite, regulates metabolism)
What is the structure of GPCRs?
7 transmembrane-spanning helices with associated G-protiens (alpha, beta, and gamma subunits)
What is the classical pathway of G proteins?
Gs and Gi stimulate and inhibit (respectively) cAMP production by adenylate cyclase
What is the non-classical pathway of G proteins?
Gq protein induces phospholipase C mediated cleavage of PIP2 to IP3 and DAG, which both contribute to downstream signaling
How can GPCR signaling be fine-tuned?
they can be endocytosed to remove them from the membrane or phosphorylated to desensitize them
What type of membrane receptor is disordered in nephrogenic diabetes insipidus?
GPCR malfunction
failure to incorporate aquaporin GPCRs into the membrane to concentrate urine
What is the general pathogenesis of Graves disease?
activating antibodies bind to the TSH receptor (a GPCR), leading to hyperthyroidism
Graves’ thyroid disease is a result of one of the following:
a) nuclear receptor gain of function mutations
b) activating antibodies to thyroid hormone receptors
c) stimulating antibodies to the TSH receptor
d) a somatic activating mutation to the TSH receptor
c) stimulating antibodies to the TSH receptor
a gain of function mutation to a GPCR
Nuclear receptors are activated by ligands that:
a) are peptides and large proteins
b) are small molecules derived from the human genome
c) water soluble ligands derived from amino acids
d) lipophilic compounds molecules that are not directly derived from the genomic sequence
d) lipophilic compounds molecules that are not directly derived from the genomic sequence
To what class of receptors does the insulin receptor belong?
a) nuclear receptor
b) tyrosine kinase
c) GPCR
b) tyrosine kinase
