Cell Signaling Flashcards
cell-surface receptor
on plasma membrane
small hydrophilic signaling molecues - can’t pass PM
cytoplasmic domain sends signals
intracellular receptors
ligand is hydrophobic and bound on a carrier protein - can cross plasma membrane into nucleus
Nitric Oxide gas
vasodilator!
nerve –> endothelial cell, rapid diffusion across cell membrane
Nitroglycerin –> NO
NO binds to guanylyl cyclase which turns GMP to cGMP –> rapid relaxation of smooth muscle cell
Phosphodiesterase Type 5- breaks cGMP back to GTP - if inhibited - more cGMP, more vasodilation (viagra)
Phosphodiesterase 5
breaks cGMP back to GTP
if inhibited –> vasodilation!
viagra
steroid receptor domains
- ligand binding
- DNA binding
- transcription activating
(also inhibitor bind)
if steroid binds –> inhibitor falls off –> can bind DNA
antiestrogens
Tamoxifen
like estrogen binds to receptor but binds repressors and turns off transcription
breast cancer –> estrogen –> growth
ion channel linked receptors
ligand - change permeability! receptor is an ion channel
GPCR
largest family of receptors
pass throguh cell membrane many times
alpha - bound to GTP or GDP - to activate - activate target protein
alpha has intrinsic GTPase activity –> takes off GDP and turns self off
alpha proteins bind diff proteins, bind diff receptors - specificity
CCR5
cytokine receptor - HIV uses it to get into cells
some w mutation can’t be infected!
Tyrosine Kinsase
phophorylates on OH
Insulin, EGF, PDGF
MOST
Serine/threonine kinase
TGF beta
cytokine receptor
cytosolic kinase associates w the receptor
phosphorylation
phosphate from ATP
negative - changes shape
binding site for other proteins –> recruit proteins to activate
TGF
signals via surface serine/threonine kinase receptor
ligand binds –> dimerize –> activate kinase domain by transphosphorylating –> smad 2 or 3 localized and phosphorylated (trnascrotion factor) –> binds to smad 4 –> goes to nuclues and activates transcription of target genes
fibrosis
fibrosis - turning genes such as collagen and fibronectin and inhibiting proteases that break down matrix
tumor suppressor
turning on genes involved in growth arrest and inhibition of genes that are pure growth
RTK signaling
inactive in membrane
signal binds –> dimerize –> phosphorylate tyroside residues by cross phosphorylation (many times - activate kinase so more active) –> recruits proteins with SH2 domains (signalling proteins that bind to phosphorylated tyrosines) –> recruit range of singlal molecules
SH2 domain
proteins have diff catalytic activities - which domain it is recruited to
SH2 binding - allows protein to dock on phosphorylated tyroside resides on other proteins - docking only
has bind site for phosphotyroside and for AA side chain - specificity for which Tyr = which signal molecule is recruited
biological outcome is related to the combination of SH2 domain containing proteins recruited
PLC gamma
RTK bind ligand - phosphorylate tyrosines –> PLC docks on SH2 domain –> enables kinase to tyrosine phosphorylate PLC and put it’s next to PIP2 hich is it’s substrate (needs to cleave)
Jak2 kinase
binding of interferon –> cross links adjacent receptors –> Jaks on receptors cross phosphorylate each other on tyrosines –> activated Jaks phosphorylate the receptors on tyrosines –> activated jaks phosphorylate cytoplasmic tyrosine kinase
Ras
first oncogene discovered!
mitations in normal genes result in constitutive activation of proteins encoded by these genes
proto-onco Ras mediates bio processes and activated by receptors - like cell growth and differentiation
EGFR binds –> RTKs phosphorylate each other –> Grb2 docks by SH2 domain –> SH3 domain binds Sos –> acivates Ras which is a transcription factor –> activates MAP kinase pway for growth
