Cell Signaling

Question 1

Roughly 40% of drugs are directed agonists or antagonists for which type of receptor?

Answer 1

G protein coupled receptor

Question 2

Activating and inhibiting _____________ is the basis of synaptic transmission of nerve impulses.

Answer 2

Ligand activated plasma membrane ion channels

Question 3

T/F: Ligand activated ion channels in the plasma membrane produce a graded potential.

Answer 3

True

Have multisubunit proteins

Question 4

In plasma membrane ligand activated ion channels, they typically let in Na+ to ____________ the cell, and let in Cl- to ___________ the cell.

Answer 4

Depolarize; hyperpolarize

Question 5

What are some ligands that will depolarize a ligand-activated ion channel in the plasma membrane? Hyperpolarize?

Answer 5

Depolarize: acetylcholine, serotonin, glutamate

Hyperpolarize: glycine, GABA

Question 6

Name four ways that drugs can affect plasma membrane ligand activated ion channels.

Answer 6

1. Mimic or block actions of neurotransmitters
2. Block the channel
3. Affect NT reuptake
4. Affect NT metabolism

Question 7

What is the most notable ligand activated ion channel found in the organelles?

Answer 7

IP3-mediated channel that will release Ca++ from the ER

Question 8

800 functional genes encode ___________.

Answer 8

G protein coupled receptors (400 in nose)

Question 9

G protein coupled receptors involve a single polypeptide with ____________.

Answer 9

7 transmembrane alpha helices

Question 10

How do agonists activate GPCRs?

Answer 10

Bind to the GPCR -> alter the proteins conformation -> leading to the activation of a trimeric G protein

Question 11

What happens inside of the cell after a ligand binds to a GPCR?

Answer 11

1. GTP takes place of GDP in complex
2. Complex falls into to parts: Galpha and GbetaGgamma
3. Both parts of the complex participate in cell signaling events

Question 12

What are the steps in the G protein cycle that bring the receptor back to its starting point?

Answer 12

1. The GTP in the Galpha is hydrolyzed to GDP via intrinsic GTPase
2. After hydrolysis the complex reassembles

Question 13

Which is the major part of the G protein complex?

Answer 13

Galpha

Question 14

_______ increases adenylate cyclase activity and ______ decreases adenylate cyclase activity.

Answer 14

Galpha(s); Galpha(i)

Question 15

Describe GPCR activation of PKA.

Answer 15

Galpha(s) activates adenylate cyclase which converts ATP to cAMP which activates PKA leading to phosphorylation of many proteins

Question 16

How can GPCR activity lead to changes in gene expression in cells?

Answer 16

GPCR activation leads to PKA phosphorylation of transcription factors

Question 17

Which liver activity is mediated by PKA?

Answer 17

Glycogenolysis (mobilization of glucose)

Question 18

What is the effect of GPCRs activating phospholipases?

Answer 18

Release of signaling molecules embedded within phospholipids of the membrane

Question 19

What are the major actions of Galpha (i and o)?

Answer 19

Decrease adenylate cyclase activity and increased phospholipase A2

Question 20

Arachidonic acid is the source of ___________ and ___________.

Answer 20

Eicosanoid signaling molecules; prostaglandins

Question 21

Galpha(q) can activate ______________ which will release DAG and IP3 as signaling molecules.

Answer 21

Phospholipase Cbeta (PLCbeta)

Question 22

What is the substrate that PLCbeta cleaves into DAG and IP3?

Answer 22

PIP2

Question 23

What is the effect of IP3 being released into the cell?

Answer 23

Ca++ is released from ER -> Ca++ binds to calmodulin -> altered Ca++/colmodulin complex is able to interact and activate effector proteins

Question 24

What are two examples of proteins activated by Ca++/calmodulin complex?

Answer 24

1. Ca/calmodulin dependent protein kinase

2. Nitric oxide synthase

Question 25

How does DAG activate PKC?

Answer 25

PKC needs Ca++ to activate. DAG allows PKC to bind Ca++ tighter so it can work in lower Ca++ concentrations

Question 26

T/F: The agonist-GPCR complex can activate other trimeric G proteins.

Answer 26

True Will eventually turn off by desensitization

Question 27

What are the four major steps in the desensitization and endocytosis of GPCRs?

Answer 27

1. Phosphorylation by a GRK 2. Binding by beta-arrestin 3. Formation of clathrin-coated pit 4. Endocytosis

Question 28

What are the two fates of GPCR that are endocytosed?

Answer 28

Recycling or degradation

Question 29

What are some common ligands to receptor tyrosine kinases?

Answer 29

Growth factors, differentiation factors, cytokines

Question 30

Binding of ligands to a RYK leads to _________ of the receptor.

Answer 30

Dimerization

Question 31

T/F: Some RYKs form homodimers and some form heterodimers but they do not form both.

Answer 31

False Some also form both

Question 32

Describe the process of activation via RYK?

Answer 32

Ligand binds -> dimerization of receptor ->transphosphorylation -> docking of signaling molecules -> various signaling cascades

Question 33

Describe the JAK-STAT example of a RYK signaling cascade.

Answer 33

JAK kinase phosphorylates receptor after ligand binds -> STAT protein binds to receptor -> phosphorylation of STAT by JAK kinase -> dimerization of STAT protein -> STAT moves to nucleus and activates genes

Question 34

T/F: STAT monomers contain two domains (SH2 and tyrosine) that can be phosphorylated.

Answer 34

True

Question 35

STAT proteins mediate biological responses to which ligand?

Answer 35

Cytokines

Question 36

Nuclear hormone receptors typically bind what molecule as a ligand?

Answer 36

Steroid hormones (Glucocorticoids, mineralcorticoids, testosterone, estrogens, progesterone) *also vitamin D, retinoic acid, thyroid hormone

Question 37

Describe the process of activation via a class 1 nuclear receptor.

Answer 37

Ligand binding induces complex to fall apart, form a homodimer, and bind to specific DNA element -> binds to coactivators to stimulate transcription

Question 38

T/F: Class I nuclear receptors exist as a complex with heat shock proteins in the absence of a ligand.

Answer 38

True

Question 39

What are some examples of ligands for class 1 nuclear receptors?

Answer 39

Glucocorticoids, progesterone, estrogens, androgens

Question 40

T/F: Class 2 nuclear receptors bind to target DNA in absence of ligand.

Answer 40

True

Question 41

What is a big difference between class 1 and class 2 nuclear receptors?

Answer 41

Class 2 binds to corepressors and represses transcription in the absence of a ligand Class 1 does not bind to DNA targets until bound to a ligand

Question 42

What happens to class 2 nuclear receptors when bound to ligand?

Answer 42

Switch from binding corepressors to binding coactivators -> activates transcription

Question 43

What are some examples of ligands for class 2 nuclear receptors?

Answer 43

Thyroid hormone, retinoic acid, Vitamin D