Week 2 Flashcards
Endocrine chemical messenger cells:
secrete hormone into the blood
specific target cells that can be very far away
usually high concentrations to react all over body (insulin, glucagon, cortisol)
Paracrine chemical messenger cells:
Actions performed on nearby cells
Only need low amounts of secretions to only act locally
Location of cells plays a role in specificity of response
Autocrine chemical messenger cells:
Act on the cell from which it is secreted or on nearby cells that are of the same type
Most autocrine cells are also paracrine cells
Hydrophobic chemical messengers are specific for _______ _______
Intracellular receptors (Ex: Steroid hormones - cortisol) - also called Lipophilic hormones
For intracellular receptors and hydrophobic messengers like cortisol, are they fast or slow to change cellular phenotype after eliciting a transcriptional response?
Slow
______ chemical messengers are specific for plasma membrane (cell surface) receptors.
Hydrophilic
What are the examples of the Cell surface membrane receptors?
Serine/threonine kinases (heterodimirical)
Tyrosine kinases (insulin)
Jak-STAT signaling
G-protein coupled receptors
How do cell surface membrane receptors change enzyme activity ? direct or indirect? what type of interactions? Fast or slow to change phenotype?
Direct
Protein-protein interactions
Fast to change phenotype
What does cortisol need to attach when traveling in bloodstream due to it being hydrophobic?
Attach to serum albumin (plasma protein) and steroid hormone binding globulin
Where is cortisol released from?
Adrenal Cortex and diffuses into bloodstream
What does Cortisol bind to?
Cortisol receptors (intracellular) in the cytosol after diffusion through plasma membrane
What are the 3 domains of the Cortisol receptors?
- Transactivation Domain
- DNA binding domain
- Ligand binding domain
What does the Ligand binding domain on Cortisol receptors do?
Causes conformation change in receptor
- Dimerization of receptors
- Exposes a nuclear translocation signal- allows hormone receptor to cross the nuclear membrane into nucleus
What does the Hormone receptor complex for Cortisol do once in the nucleus?
Acts as transcription factor
-Binds to portion of DNA called the hormone response element or GRE (glucocorticoid response element)
What is the name or the section that the hormone receptor complex for cortisol binds to once in the nucleus?
Glucocorticoid response element (GRE)
-or called hormone response element
What happens after the Glucocorticoid response element (GRE) is bout to by the cortisol receptor hormone complex once inside nucleus?
Induction (increase) or Repression (decrease) in gene transcription depending on the location of the GRE that is bound on DNA
How is the signal that the cortisol receptor induces terminated? where in the chain of events?
Cortisol concentration is lowered by the liver destroying cortisol (degrading) so that less signaling occurs
Where are Tyrosine Kinase receptors (insulin signaling)?
TK receptors are in the cell membrane (transmembrane)
-Function as dimmers
What happens after the insulin hormone binds to the receptor?
Autophosphorylation occurs on inner side of receptor
IRS (insulin receptor substrate) protein is then bound to receptor and forms a phosphorylated tyrosyl residue (tyrosine) at multiple sites
What happens during the tyrosine kinase insulin pathway after the tyrosyl residue is phosphorylated on the IRS proteins?
Multiple different proteins can bind to different phosphorylated tyrosyl residues
What different proteins can bind to the phosphorylated tyrosyl residue on the IRS protein that is bound on the intermembrane side of the insulin hormone receptor?
PI-3 kinase (Phosphoinostitol 3 Kinase)
PLC (Phosophlipase C)
Grb2
(all have SH2 domain that binds to different sites on phosphate group of IRS protein)
What does the Grb2 bind in the specific Insulin pathway (Tyrosine Kinase pathway example)?
Activated Grb2 binds to GAP1 (or a SOS-GEF) which is connected to a PIP in the membrane
What happens to the SOS-Ras complex after is has a conformation change in the general Tyrosine Kinase pathway and GDP was exchanged for GTP?
Ras-GTP binds to Raf to activate it
What is the purpose of activating Raf in the general Tyrosine kinase pathway by the Ras-GTP complex?
Activated Raf is the first step in a MAP-kinase cascade that can lead to a change in gene transcription