Chemical signal1

Question 1

3 main types of chemical signals?

Answer 1

1. Endocrine
2. Paracrine
3. Authocrine

Question 2

Endocrine

Answer 2

The chemical agent(inducing agent) acts at a site distant from the secretory site

Question 3

Paracrine

Answer 3

The chemical agent acts at a site close to secretory site
Ex: cytokines that are released by immune system cells and mediate the immune response.
Juxtacrine, especial type of paracrine.

Question 4

Juxtacrine

Answer 4

The chemical agent acts at a cell that is in contact with the secretory cell

Question 5

Autocrine

Answer 5

The chemical agent acts on the cell that secreted it

Ex: growth factor, like various growth factor(GFs)

Question 6

What do chemical messenger require?

Answer 6

Inducing agent(ligand)
Recepto

Question 7

Inducing agent(ligand)

Answer 7

The substance that is secreted to produce an effect at a target(chemical messenger:1st messenger

Question 8

Receptor

Answer 8

-Binds the ligand at the target cell.
Intracellular
Extracellular
-upon binding the ligand, the receptor must activate some preprogrammed cellular process.
May utilize 2messenger system(ca,camp,cGMP) that relay the signal from the receptor to the appropriate cellular location

Question 9

Intracellular

Answer 9

For lipid soluble messengers(steroid hormone)

Question 10

Extracellular

Answer 10

For lipid insoluble

Found on the plasma membrane surface for agents that can’t diffuse into the cell(integral membrane protein)

Question 11

Multiple signals maybe integrated(pathway cross-talk)

Answer 11

1-One receptor activates multiple pathways
2-different receptor activates the same pathway
3-different receptor activates different pathway;one pathway affects the other.

Question 12

Receptor down regulation

Answer 12

If a signaling mechanism is active for a prolonged period of time, the system adopts by:
A)decreasing the number of receptor(endocytosis)
B)desensitization-receptor is altered in some reversible fashion(phosphorylation)to make it less functional
A type of negative feedback to prevent overstimulation

Question 13

Agonists and antagonists(other chemical agents that bind To the receptor)

Answer 13

Agonists activates the receptor ( mimetics)

Antagonists inhibit the receptor

Question 14

Signal amplification

Answer 14

Second messenger system allow for amplification of the signal
Ex: epinephrine induced breakdown of glycogen
A single molecule of epinephrine(adrenaline) results in the activation of 10^6 molecules of glycogen phosphorylase

Question 15

Which chemical messenger do not require a second messenger system?

Answer 15

Steroid hormone

Question 16

Steroid hormone

Answer 16

• Lipid soluble(can enter the target cell cytoplasm)
• Bind to an internal receptor(in most cases)
• Nuclear receptors(will influence gene expression)
• cytoplasmic receptors(will then travel to nucleus)
• steroid hormone-receptor complex directly influences gene expression to exert an effect

Question 17

Steroid hormone process

Answer 17

1. steroid hormone diffuse into cell
2. binds to receptor
3. hormone-receptor complex enters into the nucleus(must have NLS)
4. hormone receptor complex interacts with DNA(must have a DNA binding domain and transcription factor)
5. altered gene expression
6. altered protein content of cell
7. generally have relatively slow, long lasting effect

Question 18

The general flow of information during cell signaling

Answer 18

1. receptor ligand binding in 1st messenger
2. signal transduction via second messenger and cellular response in cytosol
3. change in gene expression in nucleus

Question 19

Membrane receptor linked cell signaling pathway

Answer 19

Result in activation of second messenger(Intracellular messenger)
CAMP
IP3
DAG
Ca2+
NO

Question 20

Specific membrane receptor-linked second messenger pathway

Answer 20

G-protein linked receptor

Question 21

G-protein linked receptors

Answer 21

• the receptor interacts with a G-protein(guanine-nucleotide binding protein)
• the G protein then regulates some target protein
• the G protein is found on the cytosolic side of the plasma membrane
• thus 3 main components:
  1. receptor(many types:depends on ligand):membrane spanning
  2. G-protein: cytosolic side
  3. target protein (adenyl cyclase,many others):membrane spanning or cytosolic
• 7 transmembrane domains
• binding site for ligand(messenger)
• cytosolic loop & domains that interacts with G-protein
• multiple regulatory sites(GRK phosphorylation sites)

Question 22

2 classes of G-proteins

Answer 22

Large heterotrimeric G-protein

Small monomeric G-protein

Question 23

Large heterotrimeric G-proteins

Answer 23

-alpha,beta,and gamma subunit(1 each)
-collectively form G alpha,beta, and gamma timer
..G alpha binds GDP or GTP
Maybe stimulatory-G stimulatory alpha activate target protein(adenylyl cyclase)
Maybe inhibitory-G inhibitory alpha inhibit target protein
Maybe other-G other alpha

Question 24

Small monomeric-G protein

Answer 24

Consist of a single protein (Ras family members)

Similar to G alpha

Question 25

G-protein receptor function

Answer 25

1. resting state: receptor is not bound to ligand: G alpha subunit is bound to GDP and associated with G beta,gamma. 2. ligand binds receptor, the receptor binds a G protein;G alpha releases GDP and acquires GTP 3. G alpha and beta,gamma subunits separate 4. G protein subunits activate or inhibit target proteins, initiating signal transduction events. 5. The G alpha subunit hydrolyzes it's bound to GDP,becoming inactive 6. subunits recombine to form an inactive G protein

Question 26

Some G proteins act to elevate cAMP via?

Answer 26

Adenylyl cyclase

Question 27

If the target of the G-protein is adenyl cyclase what happens?

Answer 27

1. Ligand binding causes the alpha subunit to bind GTP and become activated 2. If then dissociates in its activated form to adenyl cyclase(A) 3. activated Galphs then activates adenyl cyclase 4. CAMP is made from ATP by adenyl cyclase

Question 28

The second messenger,cAMP has many cell specific effects:

Answer 28

- Epinephrine binds to a G-protein coupled receptor(beta adrenegic receptor) and induces increases in cAMP(second messenger) - the influence of cAMP is dependent on cAMP activated proteins(pka) - the cellular effects are dependent on the resident proteins that are activated by cAMP and pka(various phosphorylase and kinase)

Question 29

Another G protein target is..

Answer 29

Phospholipids C

Question 30

Phospholipase C

Answer 30

Catalyzes the formation of IP3 and DAG from PIP2 activated via Gq IP3 and DAG are both second messengers

Question 31

Gq

Answer 31

The G protein that activates Phospholipase C

Question 32

Function of Phospholipase C

Answer 32

1. A receptor is activated by the binding of its ligand. The receptor ligand complex associates with the G protein Gq,causing displacement of GDP by GTP and the dissociation of the alpha,beta gamma subunits. 2. the GTP-Galpha complex binds go Phospholipase C, activating it and causing cleavage of PIP2 into IP3 and DAG 3. IP3 is released into the cytosol where it triggers calcium release 4. DAag remains in the membrane, where it activated protein kinase C

Question 33

Cytosolic ca

Answer 33

- 2nd or 3rd messenger - because ca is a ubiquitous cellular messenger,it's levels are tightly regulated(typically at very low concentration inside the cytoplasm)

Question 34

What proteins help to regulate cytosolic ca2+

Answer 34

- IP3 induced ca2+ channel in ER - ryanodine ca2+ channel at the ER - ca2+ channels at the plasma membrane - ca2+ pumps at the ER - ca2+ pumps at the plasma membrane - Na/ca2+ exchanger at the plasma membrane

Question 35

Ca2+ effector proteins

Answer 35

Calcineurin | Calmodulin

Question 36

Calcineurin

Answer 36

Ca2+ activated protein phosphotase

Question 37

Calmodulin

Answer 37

Relatively ubiquitous,cytosolic calcium binding protein Activates many down steam target proteins Binds 1 ca2+,calmodulin activates various target protein

Question 38

EF hand domain

Answer 38

Specific helix-loop-helix motif for ca2+ binding many EF-hand proteins