Signaling hormone is transported in the blood. Name the hormone type. Give the relative half life as well.
Endocrine hormones
-short term, half life on minute scale
-act on far away signaling
This signaling hormone diffuses to neighboring target cell of a different cell type. Give the relative half life as well.
Paracrine hormones
-local signaling -short lived signal
What is type of hormone is testosterone?
Paracrine hormones
– Leydig cells synthesize and secrete testosterone induces spermatogenesis by acting on Sertoli and germ cells
Secreting cells express surface receptors for this signal hormone or release to cells of the same type. What types of proteins are they commonly found as?
Autocrine hormones
– Commonly found as chemokines
– Growth factors in cancer cells
What type of signaling hormone is interleukin-1?
What produces them and why?
Autocrine
Interleukin-1 is produced by T-lymphocytes which promote their own replication in immune response
– Growth factors in cancer cells
What type of hormone is heparin-binding epidermal growth factor? Where does it bind?
Justacrine
HB-EGF binds to EGF receptor in Immune cells
Hormone signals that cannot penetrate the cell membrane.
Hydrophilic Interact with cells at specific receptors.
Examples of hydrophilic signaling.
Epinephrine, insulin, glucagon etc
What are second messengers derived from? What is the half life?
Generally small and derived from AA, polypeptides or through lipid metabolism
Have short half-lives, about seconds to minutes.
What are two receptors involved in hydrophilic signaling?
Receptor tyrosine kinases (RTKs)
G protein - coupled receptors (GPCRs)
Hormone signals that pass through the membrane of the target cell.
Lipophilic signals
Examples of lipophilic signals.
Steroid hormones, thyroid hormone and retinoids.
What do lipophilic signals bind to?
Receptor proteins inside the cell. These can be in the nucleus or the cytosol.
Cytoplasmic receptors are what type of receptor?
Lipophilic
How do cytoplasmic receptors exist in an inactive state? By what mechanism are the activated
Bound to HSP 90.
Ligand binds -> HSP 90 dissociates -> hormone-receptor complex binds to hormone response element in promotor region of DNA
What are nuclear receptors in signaling? How are the acted upon by hormones?
Lipophilic signaling receptors, already present in nucleus and bound to DNA. Hormone allows for interaction with additional proteins and activates the complex.
What is the half-life of lipophilic signals?
Long half-lives (hours to days)
Name some examples of lipophilic signals.
Steroid hormones, thyroid hormones, and retinoids.
What are some ligand gated ion channels?
nAChR, GABAa, 5-HT3, GlyR
Name the components of a G Protein coupled receptor.
Extra cellular domain (ECD)
Trans Membrane domain- composed of 7 alpha helices
Intracellular Domain (ICD)
What does the Extracellular domain in a GPCR do?
Binds to the signal, this causes conformational change of GCPR, allowing the ICD to become active
What does the Intracellular domain in a GPCR do?
Interacts with G proteins, upon conformational change induced by ECD it activates G protein by triggering exchange between GDP and GTP.
Utilizes Gaunine Exchange Factor (GEF)
When is G-protein active? How does this occur?
When GDP is exchanged for GTP by the intracellular domain of GCPR. This occurs via the guanine nucleotide exchange factor (GEF).
What happens after activation of the trimeric G-protein?
The GTP-bound alpha subunit separates.
How does G-protein turn back to inactive state? How is this action accelerated?
The intrinsic GTPase activity of G protein hydrolyzes it's bound GTP into GDP and phosphate.
Accelerated via the GTP-ase activating protein (GAP).
What does Gs do? Whats it bind to?
Gs stimulates adenylate cyclase through binding a signal molecule.
What does adenylate cyclase do once it becomes activated?
Activated Gs -> activates Adenylate cyclase -> up regulation of cAMP -> PKA becomes active -> target proteins have activity altered.
What does Gt do? Whats it bind to?
Stimulates cGMP phosphodiesterase. Light binds to it.
What does cGMP phosphodiesterase do?
Changes cGMP to 5'-GMP
What does Gi do? Whats it bind to?
Inhibits adenylate cyclase directly, through the binding of a signal molecule.
