LM17.1-Cell Signaling Intro Flashcards
(10 cards)
What is a signal and what are the properties needed for a signal to generate a a sufficient response?
1) a signal is something that elicits a response
2) mode of transmission and a target (receptor, affinity, etc.)
Can you demonstrate how secondary messengers cause amplification?
Vision Mechanism
1) During dark state, one photon of light (1st messenger) activates one rhodopsin molecule
2) which activates hundreds of transducin molecules per second
3) each transducin activates PDE6 which hydrolyzes 1000 cGMP to GMP per sec
4) which closes channels and causes cell to be hyperpolarized
Explain the G-protein receptor (GPCR)?
- most abundant and diverse receptors (can bind almost anything)
- about 33-50% of all current marketed drugs target these receptors
1) extracellular ligand binds, changing the cytosolic portion conformation
2) conformational change activates G-protein (alpha-subunit that binds GTP)
3) G-protein (alpha-subunit) then relays signal
4) afterwards, alpha-subunit hydrolyzes GTP inactivating itself
5) Another protein, RGS accelerates inactivation
How do receptor tyrosine kinases work (mechanism)?
- they are essentially transmembrane kinases (they are enzymes)
- they bind to growth factors and hormones
- once ligand binds, RTKs dimerize and kinase portion is activated (phosphorylating Tyr on cytoplasmic region of receptor)
- other signaling proteins that promote cell growth/proliferation and inhibit apoptosis assemble to get phosphorylated
What is the role of intracellular receptors? How do they work?
1) these receptors are inside of the cell (cytosol) and bind lipid soluble (hydrophobic) ligands
2) nuclear receptors (which can bind steroid, thyroid, vit D) are a type of intracellular receptor
3) GR ( a nuclear receptor) in its inactive state is bound to HSP90
4) once ligand binds, GR is activated and HSP90 leaves.
5) GR dimerizes then enters nucleus and acts as a TF
How do ions affect different signaling pathways?
PENDING
What are some examples of multiple signaling defects affecting human health & disease?
PENDING
What are the four types of receptors that can receive signals?
1) GPCR
2) Ligand-gated channels
3) Receptor tyrosine kinases
4) intracellular receptors
What happens after prolonged stimulation of a G-protein?
1) Usually when a signal is bound to it’s GPCR the G-protein remains active
2) after awhile, prolonged stimulation inactivates the GCPR (even though ligand is still bound
3) the transmembrane portion of GCPR is phosphorylated by a kinase
4) a protein called arrestin then binds to the transmembrane portion blocking its interaction with G-protein (alpha-subunit)
Why are receptor tyrosine kinases (RTK) important when discussing cancer?
1) In cancer cells, signal emission by EGF receptors (epidermal growth factor receptors are a type of RTK) is deregulated
2) thus cell grows and proliferates(tumor), has increased inhibition of apoptosis (resistance to chemo), and improves its motility (metastasis)
