CST Flashcards
What is necessary for the signal and target cell to produce?
Signal: a ligand and target: receptors specific for that ligand.
What is the electrical form of cell communication?
Gap Junctions (excitable systems in the heart connected by connexons)
What is the mechanical form of cell communication
Direct cell-to-cell contact signaling (such as intestinal crypts)
What is endocrine signaling?
Hormone signaling from a long distance through the blood (sex hormones, thyroid hormones)
What is paracrine signaling?
Paracrine factors, the signaling molecule acts on a neighboring cells, short distance, gradient factor determines outcome (i.e. Blood clotting)
What is Autocrine signaling?
Autocrine factor, cells respond to their own signaling molecule (ex t-lymphocytes drive their own proliferation)
What is synaptic signaling?
Signals between nerve cells, action potential ex:muscle stimulation
What is contact dependent signaling?
Ligand and receptor are on the cell membrane (ex intestinal crypts, absorptive/secretive cells.
Ex: fas signaling (apoptosis)
Signaling molecules
Act by binding to receptors
What are hormone signaling molecules
Steroid hormones, synthesized from cholesterol, they are hydrophobic, carried by globulins, diffuse across the plasma membrane and bind to internal receptors.
Sex hormones: testosterone, estrogen, progesterone
Corticosteroids: glucocorticoids (cortisol), mineralocorticoids (aldosterone)
How is nitric oxide (NO) used in cell signaling?
Paracrine signaling molecule
Short half life
Can diffuse across cell membranes
Alters the activity of target enzymes (guanylyl cyclase to cGMP)
Causes muscle relaxation.
Acetylcholine binds to a membrane bound receptor (ligand-receptor) and causes NO synthase to be activated (NOS). NOS uses arginine to make NO which rapidly diffuses across the membrane. No binds to guanylyl cyclase which turns GTP into cyclic GMP which allows for rapid relaxation of smooth muscle cells.
How do peptide hormone signaling molecules work?
A few to several hundred amino acids
Bind to cell surface receptors (ex: insulin, glucagon, FSH)
How do growth factors work?
Control cell growth and differentiation
Bind cell surface receptors
Ex. Nerve growth factor- survival of neurons
Epidermal growth factor: cell proliferation
PDGF: wound healing
how do neurotransmitters work?
Signaling molecules from neurons to target cells and causes a release of an action potential in neuron
Hydrophilic (unable to diffuse across the membrane alone - binds to cell surface receptor)
Ex. Acetylcholine, glycine, glutamate, dopamine.,
What are internal receptors?
Signals diffuse across the membrane and bind to internal receptor.
Hormones: estrogen/testosterone
Often targets the nucleus
How do membrane receptors mediate/work?
Bind membrane receptor
Peptide hormones: insulin
Growth factors: PDGF
Neurotransmitters: dopamine
How do nuclear receptors work
They respond to hormones (estrogen, testosterone, progesterone, cortisol)
Diffuse through the cell membrane
Bind to internal receptor in the cytosol or nucleus which causes a conformational change to make it active and it exposes DNA to NLS sites.
Transcription regulator: promote or inhibit, contain DNA binding sequences, bind to DNA regulatory site
G protein coupled receptors
Largest family of cell surface receptors
Binding of ligand to GPCR causes conformational change and activates the G protein (trimeric G protein) the alpha unit leaves the beta and gamma because the activated receptor causes bound GDP to be replaced with GTP, activating it. The beta and gamma units are also active, the beta/gamma interacts with membrane bound enzyme phospholipase C
Alpha unit interacts with adenylyl cyclase which converts ATP into cyclic AMP (cAMP) which is a secondary messenger that activates protein kinase A (PKA) aka cAMP dependent protein kinase which causes glycogen breakdown (by activating glycogen phosphorylase) and gene expression by facilitating transcription and controlling cell proliferation, survival, differentiation, and learning/memory
How does glycogen metabolism occur?
Epinephrine -> activates Gs(alpha unit) with GTP
Adenyl cyclase increase cAMP which activates PKA which activates glycogen phosphorylace and inhibits glycogen synthase
Glycogen phosphorylase takes glycogen and turns it into glucose-1-phosphate.
How do receptor tyrosine kinases (RTKs) work?
Transmembrane protein
Receptor (ligand binding)
Kinase domain which activates upon dimerization
Phosphorylation: kinases phosphorylate each other and recruit/activate downstream messengers.
Secondary adapters/messengers contain SH2 domains that bind RTKs which activate Ras(a GTP binding protein) by adding a phosphate from RTK to inactive Ras and replacing the GDP connected to Ras
Growth factors: growth, proliferation and differentiation, epidermal growth factors, and nerve growth factors.
What is Ras
Analogous to the alpha unit of trimeric G proteins
Mediates signaling by most RTKs
Molecular switch conformations- cycle between active (GTP) and inactive (GDP)
RTK and adaptor proteins: SH2-binds RTK and SH3 binds secondary protein GEF
Secondary mediators
1. Guanine Nucleotide Exchange factor (GEF) facilitates the exchange of GDP for GTP (becomes active)
2. GTPase activating protein (GAP) activates the GTPase activity (becomes inactive)
How does Ras affect cell proliferation?
When Ras is increased cell proliferation also increases, survival
Ras is implicated in 50% of colon cancers (oncogenic) mutant Ras is common in tumors, it has no GTPase activity which means it cant hydrolysis GTP to GDP which means its always active
