Cell Signaling Flashcards
which ligand will need help to pass the membrane? where will receptor be found?
hydrophilic ligand
receptor on outside of cell (has to cross)
which ligand will readily diffuse over the membrane? where will receptors be found?
Lipophilic
inside cell
i.e. steroid hormones
what controls everything at the cellular level?
cell signaling
what is the slow response?
gene expression changes
via MAP kinase
what is fast response?
alterations in function of enzyme
generation of cyclic AMP
extracellular signal binds to a specific receptor on target cells to initiate signal transduction
cell signaling
3 types of signaling
autocrine
paracrine
endocrine
autocrine
one cell feeds back on another
endocrine
distal signaling
long lasting molecules, mostly steroid hormones
low turn over rate ,diffuse
paracrine
fibroblasts below epithelium
localized signaling
same ligand has different responses
i.e. acetylcholine
steps in signal transduction (basic)
extracellular signal molecule binds to receptor protein
causes intracellular signal proteins to carry signal to effector proteins
three types of receptors
ion channel coupled receptors
enzyme coupled receptors
g protein coupled receptors
transmembrane component of G protein coupled receptor
anchors receptor
7 passes of membrane
cytoplasmic loop of g protein coupled receptor
regulatory domain
not found in RTKs
trimeric complex is inactive when…
it binds to cytoplasmic loop
becomes monomeric
heterotrimeric G proteins
guanine nucleotide binding proteins with 3 subunits: alpha, beta, gamma
what happens when G-proteins bind to cytoplasmic loop?
becomes inactive
is only monomeric g-alpha (beta and gamma are inactive)
Active form of G-Protein …
occurs when it has a GTP
creates downstream conformation changes in enzymes (2nd messengers)
2nd enzymes of the GpCR
adenyl cyclase
phospholipase C
PLC makes
makes 2nd messengers
IP3 and DAG
Adenyl Cyclase makes
makes 2nd messengers
cyclic AMP
Phosphodiesterase
converts cyclic AMP to AMP
shuts down this signaling
which 2nd messenger of GPCR is potentiating?
PLC
generates 2nd messenger
which 2nd messenger of GPCR is attenuating?
PDE
converts cyclic AMP to AMP to shut off signal (destroys second messneger)
cAMP activates…
cAMP-dependent PKA
cAMP-dependent Pka
4 subunits
when cAMP binds it attaches to regulatory parts and pushes out activated units
Cholera
failure to turn off signal (alpha subunit remains active)
unable to hydrolyze GTP so PKA continually phosphorylates channel and water is sent out
Ways to attenuate the signal of GPCR
- hydrolyze GTP on G-Alpha subunit (dropping of hormone levels)
- Remove signaling molecule
- Endocytosis and endosome activity to completely sequester or destroy the receptor
GRKs
kinase phosphorylates cytoplasmic domain to stop G-alpha
phosphorylates receptors so arresting will bind to cap and prevent GTP from binding to G alpha
arrestin protein
puts a cap on the third loop to prevent the activity of the receptor
keeps alpha- g bound to GDP
variations of G-Proteins
Gs
Gi
Gq
Gs
stimulates adenyl cyclase
Gi
inhibits adenyl cyclase
Gq
activates PLC (instead of adenyl cyclase)
phospholipase C makes what from PIP2
2 molecules, both activate PKC (and calcium)
IP3 or Dag
calcium signaling is which 2nd messenger system?
PLC to IP3 or DAG
NOT tyrosine kinase
PCK is activated by which second messenger(s)?
IP3 or DAG
PLC pathway
enzyme coupled receptors create
docking sites
dimerize instead of activate complex
what is the GEF in GPCR?
the receptor itself
what is the GEF in tyrosine kinase?
SOS
steps in tyr k.
- Ligand binds to tyrosine monomer
- tyrosine moonier aggregates –> dimerization
- Autophosphorylation
- SH2 domain of GRb2 binds to tyrosine kinase
- SH3 of GRB 3 binds to SOS
- SOS exchanges GTP for GDP from Ras
- Ras binds to Raf
Slow response of Ras-Raf example
Insulin signaling
via gene transcription
fast response of Ras-Raf pathway
Glut 4
Direct activation of enzymes that alter activity (already synthesized)
G-PRotein coupled receptor
Jak Sat
direct connection
activate Jak, Stat goes to the nuclease
Serine/Threonine
when Serine or Threonine is activated SMAD goes to nucleus