Hormone Signaling Pathways

Question 1

What time of signaling molecules are the following classified as (endocrine, paracrine, autocrine, or juxtacrine):

1. Epinephrine
2. Testosterone
3. Interleukin-1
4. Heparin-binding epidermal growth factor

Answer 1

1. Endocrine
2. Paracrine
3. autocrine
4. juxtacrine

Question 2

Epinephrine, insulin, and glucagon are examples of hydrophilic or hydrophobic signaling?

Answer 2

Hydrophilic

Question 3

Signaling molecule-receptor complex acts as a transcription factor in hydrophilic, hydrophobic or both signaling pathway?

Answer 3

In lipophilic aka hydrophobic.

Question 4

In lipophilic hormone signaling there are cytoplasmic and nuclear receptors. While nuclear receptors are on the nucleus bound to DNA, cytoplasmaic receptors reside in the cytoplasm and when bound to hormone the complex translocates to the nucleus. What keeps the cytoplasmic receptor in it’s unbound form and in an inactive form and prevented from disassociating or translocating to other places.

Answer 4

HSP 90 proteins.

Question 5

Which do you expect to have a shorter half life, lipophilic or hydrophilic medications?

Answer 5

Hydrophilic medications (seconds to minutes) 
Lipophilic medications live longer like hours to days (ex. oral contraceptives)

Question 6

What keeps a GPCR in it’s inactive form?

Answer 6

inactive form has guanosine diphosphate (GDP) bound to it’s alpha subunit which is bound to the beta and gamma subunits.

Question 7

how does a G protein become active?

Answer 7

GDP is replaced for GTP which is done by guanine nucleotide exchange factor (GEF).

Question 8

During activation which subunits (a,b,g) of the G protein are bound to the G protein itself.

Answer 8

Alpha is bound. gamma and beta are released.

Question 9

How does a g protein get inactivated?

Answer 9

It is hydrolyzes the GTP and thus goes back to it’s inactive GDP. this is does by GAP which removes a phosphate group.

Question 10

Describe the signaling pathway of Gs

Answer 10

Gs stimulates AC, which converts ATP into cAMP which then activates PKA which then goes to phosphorylate target proteins and effects target proteins.

Question 11

Describe the signaling pathway of Gi

Answer 11

Gi inhibits AC and thus decrease the amount of cAMP int he cell and thus PKA is not activated and therefore no proteins are affected.

Question 12

Describe the signaling pathway for Gt and where that signaling pathway is mainly found.

Answer 12

Gt stimulates cGMP which then activates phosphodiesterlase (PDE) which then breaks down cAMP2. this is usually triggered by light and thus is used in vision.

Question 13

cAMP is the second messenger that regulates the activity of protein kinase A (PKA), and has two regulatory subunits and two catalytic subunits. when activated the catalytic subunits disassociates to pohsphoylate target proteins. What enzyme can hydrolzye cAMP into AMP and can be inhibited by caffeine.

Answer 13

Phosphodiesterase (PDE)

Question 14

Describe the Gq signaling pathway.

Answer 14

Gq works via PLC which breaks down PIP into IP3 and DAG. IP3 goes to ER binds to the IP receptor and causes release of Ca2+. An increase of cytosolic Ca causes the cytosolic enzyme protien kinase C (PKC) to translocate tot he plasmam membrane where it is activated by DAG> Ca also binds to cytosolic protein calmodulin, forming a complex that activates Ca-calmodulin-dependent proteins which include Ca calmodulin-dependent protein kinase (CaM kinase) and myosin light chain (MLC kinase). CaM kinase can phosphorylate target proteins to alter their activities. MLC kinase can phosphorylate myosin light chain to contract smooth muscles.

Question 15

Epinephrine works via which G protein?

Answer 15

Gs. Beta-adrenergic receptors are Gs receptors.

Can also work via alpha-adrenergic receptors which are Gi receptors.

Question 16

Histamine H2 receptors are what kind of receptor?

Answer 16

Gs receptors.

Question 17

Describe the primary structure of insulin.

Answer 17

Composed of two peptide chains referred to as the A chain and B chains linked together by two disulfide bridges and an additional disulfide is formed within the A chain.

Question 18

In it’s tertiary structure insulin contains what metals in it’s center?

Answer 18

Zinc.

Question 19

Inactive insulin is stored in what form?

Answer 19

Hexamer.

Question 20

Active insulin is stored in what form

Answer 20

monomer

Question 21

When there is high glucose, the preproinsulin gene is activated and and transcribed and mRNA is formed which enters the ribosomes to become preproinsulin. WHere does the preproinsulin go next and what happens there?

Answer 21

Goes to ER and it’s pro part is cleaved off and becomes proinsulin.

Question 22

Where does proinsulin become insulin?

Answer 22

in the Golgi

Question 23

When insulin is released, it is not released alone, but with _.

Answer 23

C peptide

Question 24

Describe the insulin secretion.

Answer 24

1. glucose comes inside the beta cells via GLUT2.
2. Glucose participates iin glycolysis and then TCA cycle and then makes ATP
3. when the ratio of ATP to ADP is increased it inhibits the K channels which depolarizes the membrane which brings Ca from outside to inside the cell via Ca channel
4. Ca inside the cell causes fusion of the granules to the cell membrane and releases insulin.

Question 25

When insulin binds to it’s receptor what phosphorylates the receptors?

Answer 25

Autophosphorylation.

Question 26

What phosphorylates IRS-1 during insulin signaling.

Answer 26

Phosphotyrosine residues recognize and bind to insulin receptor which phosphorylates it.

Question 27

Once IRS-1 is phosphorylated, what is the next step?

Answer 27

Binds to GRB-2 initiating the transcription of rAS and MAP kinase pathway which goes to transcribe glucokinase. GLucokinase phospharylates glucose in the first step of glycolysis and gycogen synthesis.

Question 28

In the RAS-independent insulin signaling pathway, phosphoarylated IRS1 recruits what kinase?

Answer 28

Phosphoinositide 3 kinase (PI3) which phosphorylates phosphoinostides to from IP3 and PIP3 which stimulates the recruitment of protien kinase B.

Question 29

In the RAS independent pathway, Which kinase plays a role in the insulin-induced movement of glucose transporter (Glut 4) from cytoplasm to plasma membrane of muscle and adipose cells.

Answer 29

PKB

Question 30

Which kinase promotes gycogen synthesis by phosphorylating and inhibiting glycogen synthase kinase?

Answer 30

PKb

Question 31

With increased phosphorylation of serine instead of the tyrosine in the ser/thr kinase in the IR and IRS, does what to the IRS, inhibit or activate?

Answer 31

Inhibit. which is a possibility for insulin resistance.

Question 32

Under fed conditions, insulin lowers blood glucose by

Answer 32

1. promoting glycogen synthesis
2. stimulating glycolysis,
3. inhibiting the activity and synthesis of enzymes for gluconeogenesis.

Question 33

How does epinephrine stimulate breakdown of glycogen?

Answer 33

epinephrine promotes glucagon secretion. Glucagon then breakdown glycogen.

Question 34

What are 3 major domains of a nuclear receptor?

Answer 34

Activation function 1 domain (AF1)
DNA binding domain (DBD)
ligands binding domain (LBD)

Question 35

ER-alpha is expressed most abundantly where?

Answer 35

In female reproductive tract (especially in the uterus, vagina, and ovaries), in mamma gland, hypothalamus, endothelial cells, and vascular smooth muscle.

Question 36

ER-beta is mostly expressed where?

Answer 36

Prostate and ovaries, with lower expression in lung, brain, bone and vasculature.

Question 37

How does Tamoxifen inhibit ER?

Answer 37

Tamoxifen is a ER antagonist that binds to ER and the dimerization and recruits co repressors such as NcoR. NcoR recruits histone deacetylase that act on histone proteins to stabilize nucleosome structure and prevent interaction with GTA.