Receptors and Cell Signaling Flashcards
(34 cards)
Why is cell signaling so important? Do cells talk?
Communication occurs between all cells. Signaling is the basis for normal cell growth, division and homeostasis.
What do errors in cellular signaling cause?
Cancer, diabetes, autoimmunity
Main steps in cell signaling?
- Signaling cell secretes signaling molecule (LIGAND) in response to stimulus
- Ligand is transported to target cell where it binds to a protein (RECEPTOR)
- Ligand-receptor activates or inhibits pathway (EFFECTORS)
- Effectors alter acitivty downstream and generate secondary messengers (particular response)
- Termination of signal occurs by removing Ligand/receptor or inactivation of events
What type of signaling is Endocrine?
A hormone (signal) is secreted and transported by blood to a receptor far away, turning on cascade. Long-lasting 1/2 life EX: epinephrine released by adrenal medulla acts on heart muscle
What type of signaling is paracrine?
Paracine factor (signal) diffuses to neighboring target cells of a different cell type. Local signaling, short lived signals. EX: testosterone released by leydig cells induces spermatogenesis by acting on sertoli and germ cells.
What type of signaling is autocrine?
releases signal which bind to a receptor on the same cell, or same neighboring cells. EX: interleukin1 (chemokine) produce by T-lymphocytes promotes own replication growth factors in cancer cells
What type of signaling is direct/juxtacrine?
signal binds to receptor cell, which binds the two cells together. EX: heparin-binding epidermal growth factor binds to EGF receptor. immune cells
What are the two types of signals?
hydrophilic (water soluble) and lipophilic (fat/lipid soluble)
Characteristics of hydrophilic signaling, ex: epinephrine, insulin, glucagon?
They cannot penetrate the membrane, so bind to receptors on cell surface.. activating secondary messenger, engaging proteins to a cellular response. GPCRs & RTKs
Characteristics of lipophilic signaling (ex: steroid/thyroid hormones, retinoids)?
They CAN pass through membrane, binds to receptor in cell. Ligand/receptor acts as transcription factor TF.
Where are lipophilic receptors located?
Inside the cell, either in the cytoplasm or nucleus
How do cytoplasmic receptors get the signal to the nucleus for lipophilic ligands?
The ligand binds to an inactive complex bound to HSP90. When bound, HSP90 dissociates and receptor-complex moves to nucleus where binds to HRE (hormone response element) in promoter area of genes
How do nuclear receptors work?
They are already present in the nucleus bound to DNA, hormone (ligand) activates the complex.
How long are the half lives of lipophilic signals?
LONG half - lives (hours to days)
What are the three types receptors?
ligand-gated ion channels (GABA), G protein-coupled receptors, enzyme-coupled receptor: receptor tyrosine kinases (RTKs)
What type of protein does GPCR signaling involve, and how many proteins are in the transmembrane domain?
GPCR involve heterotrimeric G proteins (three subunits alpha, gamma, beta). There are 7 transmembrane integral proteins.
What is the generic sequence of events for GPCR signaling?
Ligand to GPCR on membrane to trimeric G protein to effector enzyme (act/inact) to 2nd messenger to target of messenger to biologic response
What is the main difference between monomeric and trimeric proteins?
Trimeric contain GEF (fuanine nucleotide exchange factor) in the complex, monomeric have to recruit them.
Specifically, what happens when a ligand binds to a GPCR which then binds to the G protein?
The now active Gprotein will exchange the GDP bound to its alpha for GTP, by using guanine exchange factor (GEF). this will separate GTP-alpha SU from beta and gamma. AlphaGTP will bind effector that produce 2nd messenger
What percent of drugs work by GPCR?
70%
What is the sequence and main contributors to Gs (activation of adenylate cyclase (AC)), used by histamine and epinephrine?
Ligand to GPCR, Gs GTPAlpha binds AC (+effector), produces cAMP (2nd messenger), binds PKA, activates. Phosphodiesterase (PDE) removes 2nd messenger & turns off
What is the sequence and main contributors to Gi (inhibits adenylate cyclase (AC)), used by epi/norepi/dopamine?
Ligand to GPCR, Gi GTPalpha binds AC (-effector) , inhibits cAMP production & PKA activation
What is the sequence and main contributors to Gt (stimulates cGMP phosphodiesterase(PDE))?
LIGHT to GPCR (rhodopsin), Gt GTPalpha binds cGMP PDE, turns cGMP to 5’-GMP, turning off. no light = turned on
What is the sequence and main contributors to Gq (activates phospholipase C), used by acetylcholine?
Ligand to GPCR, Gq GTPalpha binds phospholipase C, which breaks PIP2 into DAG and IP3. DAG to PKC (phosphorylation to alter protein activity) IP3 to ER, opens Ca channels, releasing Ca2+, activating calmodulin-dependent proteins