Lec 2.11 Cell Communication 2 Flashcards
What are examples of some targets?
Adenylyl cyclase, phospholipase C
What are some examples of 2nd messengers?
cAMP, DAG, IP3, Ca 2+
What are some examples of effectors?
PKA, PKC, gated ion channels.
What are 3 other types of signal transduction?
Tyrosine kinases, JAK-STAT receptors. Serine/threonine kinases.
What are Receptor tyronsine kinases?
Enzyme linked receptors, that add Phoshate to tyrosine on proteins
What is the enzymatic domain of Receptor tyronsine kinases?
Is in the cytoplasmic tail of the integral membrane protein
What is the importance of RTKs?
Mediate growth factor signals.
What are growth factors?
proteins released by cells to promote growth of other cells
What are the components of RTKs?
Extracellular domain. Transmembrane domain. Cytoplasmic domain.
What happens when a ligand binds to RTK?
Causes a conformational change. Induces dimerization of 2 receptor monomers. Autophosphorylation occurs. Autophosphorylation recruits other proteins to the plasma membrane. Outside event (binding to receptor) gets transduced to a response inside the cell.
RTK binds to what?
Proteins with domains called the SH2 domain.
What is Son of sevenless (SOS)?
Set of genes, in humans/fruit flies. A fly can live with a mutation that causes R7 to not be there, and they can still live.
What are the 4 steps to RTK?
- RTK binds to SH2 of Grb2. 2. SH3 of Grb2 binds to PROLINES in SOS, which then binds to Ras. 3. Ras binds to Raf. 4. Which initiates the MAP kinase cascade, that impacts gene transcription.
Which is a more direct route for impacting transcription?
JAK-STAT receptors.
What are the 6 steps to JAK-STAT receptors?
- Ligand binds to receptor. 2. Receptors dimerize, then bind to JAKs. 3. JAKs P each other. 4. JAKs P receptor. 5. Receptor binds and P’s STATs. 6. STATS separate from receptors, dimerize and enter nucleus.
What employs JAK-STAT to initiate signaling?
Erthropoeitin
What are the 3 steps to Serine-threonine receptor and Smad?
- Serine-Threonine receptor binds to ligand and forms a dimer. 2. Activated receptor (by P) binds to R-Smad and P’s R-Smad. 3. R-Smad binds to Co-Smad and moves into nucleus.
What is an example of Serine-threonine receptor?
Hepcidin.
What is hepcidin involved in?
Regulator of iron homeostasis. Hormone that deals with Iron metabolism.
What is disease Hereditary Hemochromatosis?
uncontrollable iron absorption. Leading to Iron overload and thus signal transuction disease.
What does DMT1 do?
Iron into intestinal cell
What does Ferroportin do?
Iron out of intestinal cell. Into blood.
What does Hepcidin do when iron is well stocked?
Hepcidin increases. Ferroportin decreases
What does Hepcidin do when iron is depleted?
Hepcidin decreased, Ferroportin increases
What gene is involved in Hereditary Hemochromatosis?
HFE
What does HFE do?
Found in liver, binds to transferrin receptor
What if HFE is mutated and cant bind to TfR2?
Cant turn on Hepcidin, Therefore no control of ferroportin activity.
What does lots of ferroportin lead to?
Iron overload.
HFE works with what pathway to induce Hepcidin expression?
Smad
How can a signal not be turned off?
a point mutation in codon 12 results in a change from gly to VAl and activates Ras forever.
Mutations that turn on Ras forever result in what disease?
Cancer
What is the role of Grb2-SOS-Ras-Raf in a RTK pathway?
RTK binds to SH2 of Grb2. SH3 of Grb2 binds to PROLINES in SOS, which then binds to Ras. Ras binds to Raf. Which initiates the MAP kinase cascade, that impacts gene transcription.
How is phospholipase C activated?
Through G proteins. GCPR attaches to G alpha q or G alpha0.
Describe how a mutation in HFE causes a signal transduction problem and leads to iron overloading in Hereditary Hemochromatosis?
HFE is mutated and cant bind to TfR2. Cant turn on Hepcidin, Therefore no control of ferroportin activity. Which leads to Iron overload.
