Membrane, nuclear and calcium signaling Flashcards
Describe the speed of action of peptide hormones, steroid hormones and tyrosine derived hormones.
What are the 2 main categories of membrane receptors that are used by hormones?
Are there only 2 or are there other kinds of receptors also?
What hormones bind to nuclear receptors?
Steroid hormones (cortisol, androgens, estrogens)
Thyroid hormones
Vitamins (retinoic acid, vitamin D)
True/false: steroid hormones always and only bind to nuclear receptors and peptide hormones always and only bind to extracellular receptors.
False - there are examples of peptide binding to intracellular and steroid binding to extracellular
Review the general mechanism of action of GPCRs.
What hormones act via Galpha, s mechanisms?
Epinephrine
ACTH
FSH
LH
Glucagon
PTH
TSH
Calcitonin
Review the effects of these different types of GPCRs:
- Gas
- Gai
- Gaq
- G12/13
- GBY
What are the various ways in which a GPCR signaling system can be turned off?
Describe how cholera toxin interacts with GPCRs to result in explosive diarrhea.
- Cholera toxin binds to ganglioside receptor on epithelial cell of small intestine. Toxin A then enters cell.
- Toxin A binds to Gas subunit and inhibits its GTPase activity.
- Gas has bound GTP for much longer, resulting in increased activation of AC and thus increased cAMP production
- Increased cAMP results in increased activation of PKA and thus increased protein phosphorylation that results in the prolonged hypersecretion of NaCl and water into the lumen of the GI tract causing watery diarrhea, dehydration and if untreated can lead to shock, acidosis and death
Describe how bordetella pertussis interacts with GPCRs to result in whooping cough.
Part of the pertussis toxin is able to diffuse across cell membrane of ciliated epithelial cells where it binds ADP-ribose to the Gai subunit. This causes the subunit to be locked in an inactive state. This is an inhibitory subunit, so if it’s locked in inactive state it cannot inhibit AC, resulting in increased cAMP, increased protein phosphorylation and disturbance of cellular metabolic proceses that damages the ciliated cells leading to the whooping cough.
What is pseudohypoparathyroidism?
When the end organs (bone, kidneys) are resistant to PTH signaling. The body produces PTH normally and in response to the correct signals (low Ca2+) but the organs that are responsible for responding to PTH don’t sense its presence. As such, these individuals are hypocalcemic, hyperphosphatemic, and have increased circulating PTH levels.
Review the general mechanismof receptor tyrosine kinase membrane receptor signaling.
The insulin receptor is a TKR. Describe hos this receptor works and what its ligands are.
Ligands - insulin and IGF-1
Most important to recognize the general categories. That signaling through this receptor can affect general and specific gene expression, cell growth and differentiation, glucose metabolism and general anabolism, and ultimately leads to the insertion of more glucose transporters into the membrane.
What are the 2 GENERAL kinds of disorders we should know about for TKRs?
If a person is homozygous for a loss of function mutation in the insulin receptor, what might you expect them to present with clinically?
What is PCOS?
Hirsutism = excessive body hair in men and women on parts of the body where hair is normally absent or minimal
Review the general mechanism of signaling involved in the JAK/STAT pathway.
- What signaling activities is the JAK/STAT pathway involved in?
- What important cellular events is JAK/STAT important for?
- Mutations in these receptors can result in what kinds of pathologies?
What is Laron Dwarfism?
Resistance to GH due to autosomal recessive acquisition of loss of function mutations in GH receptor. Liver needs GH signaling to produce IGF-1, so these individuals will have high GH and low IGF-1. Resistant to cancer b/c IGF-1 has mitogenic capacity so reducing its action results in decreased ability for cells to become cancerous.
Review the signaling pathways of type 1 nuclear receptors.
Steroid hormone diffuses through membrane –> binds to receptor in cytosol –> receptor dissociates from heat shock protein chaperone that was keeping it sequestered inactively in cytosol –> two receptors with bound hormone dimerize –> enter nucleus via nuclear pore –> Bind to DNA response element –> coactivator and polymerase bind –> tanscription
Review the signaling pathways of type 2 nuclear receptors.
Hormone diffuses through membrane –> enters nucleus via nuclear pore –> binds to dimerized receptor that is bound to DNA binding response element –> hormone binding results in dissociation of the corepressor that was bound to nuclear receptor –> coactivator and polymerase can now bind –> transcription
If someone has a steroid and thyroid hormone resistance syndrome, how might they present? What causes these resistances?
If someone is resistant to thyroid hormone, how might they present?
Goiter –> enlarged thyroid b/c producing a lot of thyroid hormone but body is unable to respond to it at cellular level so they appear with many of the signs of hypothyroidism
