Receptors and Ligands...

Question 1

What are the 6 enzyme-coupled receptors we discussed in MCM-1?

Answer 1

1. receptor tyrosine kinase
2. tyrosine-kinase-associated receptors
3. cytokine receptor
4. protein tyrosine phosphatases
5. receptor guanylyl cyclases
6. serine/threonine receptors

Question 2

Generally speaking what type of receptor could you classify a receptor tyrosine kinase receptor as?

Answer 2

enzyme-coupled receptor

Question 3

Generally speaking what type of receptor could you classify a tyrosine kinase associated receptor as?

Answer 3

enzyme coupled receptor

Question 4

Generally speaking what type of receptor could you classify a cytokine receptor as?

Answer 4

enzyme coupled receptor

Question 5

Generally speaking what type of receptor could you classify a protein tyrosine phosphatase as?

Answer 5

enzyme coupled receptor

Question 6

Generally speaking what type of receptor could you classify a receptor guanylyl cyclase as?

Answer 6

enzyme coupled receptor

Question 7

Generally speaking what type of receptor could you classify a serine/threonine receptor as?

Answer 7

enzyme coupled receptor

Question 8

A receptor tyrosine kinase is an enzyme tyrosine kinase receptor that binds what ligands and has what effect?

Answer 8

1. binds Growth Factors (GF) and membrane bound ligands

2. activation leads to phosphorylation of signal proteins

Question 9

A tyrosine kinase associated receptor is an enzyme tyrosine kinase receptor that binds what ligand with what effect?

Answer 9

1. binds to cytokines and interleukins

2. phosphorylation of singaling proteins

Question 10

What is the difference between the receptor tyrosine kinases and the tyrosine kinase associated receptors?

Answer 10

1. receptor tyrosine kinase bind with intracellular kinase domain.
2. TKAR associates with a soluble cytosolic kinase domain which must migrate to the receptor tail in order to continue the signal sequence.

Question 11

What role does protein tyrosine phosphatase play in the signaling pathway?

Answer 11

1. these don’t have specific ligands, but when activated will lead to dephosphorylation of phosphotyrosines.

Question 12

What is the role of the enzyme-coupled receptor, receprot guanylyl cylcase have in the signaling pathway?

Answer 12

activation by a ligand allows formation of cGMP

Question 13

What is the ligand and activaiton effect of the serine/threonine receptor?

Answer 13

1. ligand is TGF-beta

2. activation leads to Smad phosphorylation and transcription

Question 14

What are receptors that require downstream proteolysis in order to lead to transcription activation? (shuold be 3)

Answer 14

1. Notch receptor
2. Frizzled receptor
3. Patched receptor

Question 15

Notch receptor must be bound with what ligand in order to cleave its cytosolic tail and allow the tail to migrate into the nucleus to activate transcription?

Answer 15

Delta

Question 16

Notch and delta binding produces what sequence of events?

Answer 16

1. notch tail is cleaved
2. tail migrates through nuclear pore complex
3. binds and activates transcription (or assists with activation)

Question 17

Frizzled receptor must bind with what ligand in order to prevent the phosphorylation and subsequent degradation of beta-catenin, which inhibits transcription?

Answer 17

must bind with Wnt

Question 18

Frizzled binding with Wnt will set into motion what sequence of events?

Answer 18

1. beta-catenin is not phosphorylated.
2. the APC unit is attracted to the frizzled/wnt complex
3. beta-catenin (unphosphorylated) migrates into nucleus to assist with transcription activation

Question 19

To prevent the degradation of the Ci protein, the transmembrane protein Patched must be bound with what ligand?

Answer 19

hedgehog

Question 20

What are the subsequent events of Hedgehog and patched binding?

Answer 20

1. patched activates smoothened
2. preventing phosphorylation of protein “Ci”
3. unphosphorylated “Ci” helps induce transcription.

Question 21

What are some common secondary messengers?

Answer 21

1. cAMP
2. cGMP
3. PIP2

Question 22

What is a second messenger?

Answer 22

• small intracellular signaling molecule that is generated in high amounts very quickly to diffuse to various parts of the cell.

Question 23

How is cAMP formed?

Answer 23

1. ATP is acted on by adenylyl cyclase to form cAMP

Question 24

What is used to reduce the amount of cAMP?

Answer 24

cAMP phosphodiesterase

Question 25

What is the mechanism of action of how cAMP leads to convey a donwstream signal?

Answer 25

1. 4 cAMP bind to regulatory domain on protein kinase A (2 per domain) 2. Bind cAMP to the regulatory domain then releases the catalytic domain which can go on to activate whatever it needs to.

Question 26

Which enzymes are responsible for forming and degrading cGMP?

Answer 26

1. formed with GTP and guanylyl cyclase. | 2. degraded by GMP phosphodiesterase

Question 27

What are a few things that cGMP can move on to activate?

Answer 27

1. activate protein kinase 2. phosphodiesterases 3. ion channels.

Question 28

The activation of protein lipase C will convert PIP2 into what secondary molecules that will have what effect?

Answer 28

1. DAG--> protein kinase C | 2. IP3--> Ca channels opening

Question 29

Aside from being cleaved to form IP3 and DAG, PIP2 can be activated to form what other secondary messenger?

Answer 29

1. PIP3 with help from PI-3 kinase

Question 30

PIP3 activation is able to activate what kinase? What is the effect of activating that kinase?

Answer 30

1. activates Akt | 2. Akt leads to cell survival and protein synthesis.

Question 31

MAP kinases are responsible for what major process that occur within cells?

Answer 31

1. regulation of growth and differentiation.

Question 32

What is the process of MAP kinase activation?

Answer 32

1. growth factor binds (enzyme coupled receptor) 2. forms Ras-GTP 3. Ras-GTP binds with Raf 4. Ras/Raf complex (map kinase kinase kinase) activate MEK 5. MEK (map kinase kinase) then activates ERK (map kinase) 6. ERK activates nuclear OR cytoplasmic proteins

Question 33

A cytokine binds and induces the dimerization of a JAK/STAT receptor. What is the process and final outcome of the cytokine binding?

Answer 33

1. JAK phosphorylate cytoplasmic tail of the cytokine receptor 2. phosphorylated tails attract the STAT molecules which then become phosphorylated themselves. 3. The phosphorylated STAT, dimerize 4. dimer migrates into nucleus to induce transcription

Question 34

The serine/threonine receptors are bound with TGF-beta leading to form a heterodimer. What happens next?

Answer 34

1. the cytoplasmic regions phosphorylate each other 2. leads to phosphorylation of protein "Smad" 3. "Smad" migrates into nucleus to act as transcription factor.

Question 35

What is the role of NF-kappa B?

Answer 35

regulate the cell's proliferation and survival.

Question 36

NF-kappa B promotes transcription.

Answer 36

TNFR binds with TNF, FASR binds with FASL, lingands that also bind with TNFR are cytokines, GF, or PAMPS. This binding will lead to the degradation of I-k-B, allowing free and now active NF-k-B to bind with DNA and induce trnascription

Question 37

Rho is able to alter the cytoskeletal changes. Meaning this molecule can be found in areas of the cell with high levels of what?

Answer 37

actin, and Rho is activated by integrin or growth factor receptors.