Question | Answer |
Signal Transduction | Intracellular processes that allows signals to be transduced from the outer cell membrane of cells to the nucleus |
4 Classes of Cell Surface Receptors | Catalytic, Noncatalytic, Steroid Hormones, and G-Protein Coupled Receptors |
Catalytic Receptors | Tyrosine Kinases, Serine/threonine Kinases |
Noncatalytic (non-kinase) | Wnts, Hedgehogs, and Notch |
Steroid Hormone Receptors | Cytosol and Nucleus |
G-Protein Coupled Receptors | cAMP-dependent, IP3-Ca2+ calmodulin dependent |
Tyrosine Kinase Receptors Ligands | Insulin, Growth Factor, FGFs, VEGF, PDGF, EGF (Neuregulin), NGF |
Tyrosine Kinase: Intracellular Signaling Pathway | PLC Pathway, Ras/MapK (Grb2/SOS), Phosphatidylinositol-3-kinase (PI3K) pathway |
Tyrosine Kinase Receptor Pathway | Ligand binds, **dimerization, **autophosphorylation, ** and recruite SH2 |
RAS activation | Ligand binds, dimerization, phosphorylate tyrosine kinase recruits Grb2, Grb2 replace GDP w/ GTP on Ras, Ras GTP recruit Raf |
MAPK pathway through RTK | Ras binds activated Raf, Ras-GTP hydrolyze to GDP release Raf, Raf activates MEK, MEK activates ERK, ERK translocates to nucleus activates TS factors |
FGF pathway | FRS2alpha activates GRB2
GRB2 activates SOS
SOS convert Ras-GDP Ras-GTP
Ras-GTP activates Rac and Raf
Raf activates MAPKK (MEK)
MEK activates ERK
ERK phosphorylates transcription factors, turn genes on or off |
Neuregulin acts through which receptors? | Erb Receptors |
Loss of NRG1 | Leads to defective trabeculation of ventricles during heart development |
Cytokine Receptor Signaling | Has tyrosine kinase tail
When these bind have crosslinked
Autophosphorylation = recruit SH2 domain |
Cytokine Receptors and JAK/STAT pathway | When cytokine binds to its receptor
Which phosphorylate Jak
In term recruit STAT
STAT proteins kinase got phosphorylated and dimerized
Then will translocate into nucleus and activate transcription factor |
Serine-Threonine Kinase Ligands | TGFB, BMP |
Serine Threonine Kinase Receptors | TGFB Type 1, TGFB Type 2 |
Serine Threonine Kinase Intracellular Signaling | JAK1 pathway, Smad protein pathway |
When is it useful for TGFB to inhibit cell proliferation? | Useful for bone formation and growth |
TGFB signaling Pathway | Ligand binds to receptor, direct phosphorylation of serine/threonine kinase, Activated TGFB phosphorylates SMAD 3 (R-SMAD) expose NLS, Phosphorylated R-smad interacts with Co-SMAD (SMAD 4) and IMPORTIN, SMAD complex translocates to nucleus, TFE3! |
Bone Morphogenic Proteins Pathway | BMP binds to receptor, Phosphorylated receptors
1) Activate TAK1-activate MKK3/6 and then p38 JNK
2)Activate SMAD 1/4
3) P38 and SMAD 1/4 – activate transcription factor ATF-2 inside the nucleus
4) ATF-2 activate/upregulate cardiac TFs that cause ca |
NODAL | Induced a left-right asymmetry in cardiac precursors: Position heart on left side, Formation of LT and RT ventricular chambers |
Nodal Expressed on the Lt side of developing embryo by hedgehog signaling | Keeps **nodal expression on the left** |
Lefty-1 binds to receptor competing with NODAL | Signals to determine Right |
Normally: Nodal is not inhibited by lefty proteins | Will activate SMAD which activate PitX2 in the nucleus to determine leftness |
When lefty proteins binds to receptor compete with nodal factor | No signals so no transcription so no leftness |
Wnt | Blocking degradation of TS activator |
Hedgehogs | Converts transcriptional repressor into activator |
Notch | Transmitting cell-surface signals to the nucleus via proteolytic cleavage-activate Notch dependent gene TS by displacing TS repressor |
Wnt Signaling pathway complex | Wnt bind to receptor, blocking the degradation of B-cateninin (TS activator), B-catenin enter nucleus form complex w/TCF/LEF activating TS of genes = cell proliferation/transformation |
TCF | T Cell Factor |
LEF | Leukemia enhancer factor |