Lec 2.11 Cell Communication 2

Question 1

What are examples of some targets?

Answer 1

Adenylyl cyclase, phospholipase C

Question 2

What are some examples of 2nd messengers?

Answer 2

cAMP, DAG, IP3, Ca 2+

Question 3

What are some examples of effectors?

Answer 3

PKA, PKC, gated ion channels.

Question 4

What are 3 other types of signal transduction?

Answer 4

Tyrosine kinases, JAK-STAT receptors. Serine/threonine kinases.

Question 5

What are Receptor tyronsine kinases?

Answer 5

Enzyme linked receptors, that add Phoshate to tyrosine on proteins

Question 6

What is the enzymatic domain of Receptor tyronsine kinases?

Answer 6

Is in the cytoplasmic tail of the integral membrane protein

Question 7

What is the importance of RTKs?

Answer 7

Mediate growth factor signals.

Question 8

What are growth factors?

Answer 8

proteins released by cells to promote growth of other cells

Question 9

What are the components of RTKs?

Answer 9

Extracellular domain. Transmembrane domain. Cytoplasmic domain.

Question 10

What happens when a ligand binds to RTK?

Answer 10

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.

Question 11

RTK binds to what?

Answer 11

Proteins with domains called the SH2 domain.

Question 12

What is Son of sevenless (SOS)?

Answer 12

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.

Question 13

What are the 4 steps to RTK?

Answer 13

1. 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.

Question 14

Which is a more direct route for impacting transcription?

Answer 14

JAK-STAT receptors.

Question 15

What are the 6 steps to JAK-STAT receptors?

Answer 15

1. 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.

Question 16

What employs JAK-STAT to initiate signaling?

Answer 16

Erthropoeitin

Question 17

What are the 3 steps to Serine-threonine receptor and Smad?

Answer 17

1. 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.

Question 18

What is an example of Serine-threonine receptor?

Answer 18

Hepcidin.

Question 19

What is hepcidin involved in?

Answer 19

Regulator of iron homeostasis. Hormone that deals with Iron metabolism.

Question 20

What is disease Hereditary Hemochromatosis?

Answer 20

uncontrollable iron absorption. Leading to Iron overload and thus signal transuction disease.

Question 21

What does DMT1 do?

Answer 21

Iron into intestinal cell

Question 22

What does Ferroportin do?

Answer 22

Iron out of intestinal cell. Into blood.

Question 23

What does Hepcidin do when iron is well stocked?

Answer 23

Hepcidin increases. Ferroportin decreases

Question 24

What does Hepcidin do when iron is depleted?

Answer 24

Hepcidin decreased, Ferroportin increases

Question 25

What gene is involved in Hereditary Hemochromatosis?

Answer 25

HFE

Question 26

What does HFE do?

Answer 26

Found in liver, binds to transferrin receptor

Question 27

What if HFE is mutated and cant bind to TfR2?

Answer 27

Cant turn on Hepcidin, Therefore no control of ferroportin activity.

Question 28

What does lots of ferroportin lead to?

Answer 28

Iron overload.

Question 29

HFE works with what pathway to induce Hepcidin expression?

Answer 29

Smad

Question 30

How can a signal not be turned off?

Answer 30

a point mutation in codon 12 results in a change from gly to VAl and activates Ras forever.

Question 31

Mutations that turn on Ras forever result in what disease?

Answer 31

Cancer

Question 32

What is the role of Grb2-SOS-Ras-Raf in a RTK pathway?

Answer 32

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.

Question 33

How is phospholipase C activated?

Answer 33

Through G proteins. GCPR attaches to G alpha q or G alpha0.

Question 34

Describe how a mutation in HFE causes a signal transduction problem and leads to iron overloading in Hereditary Hemochromatosis?

Answer 34

HFE is mutated and cant bind to TfR2. Cant turn on Hepcidin, Therefore no control of ferroportin activity. Which leads to Iron overload.