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Cell Physio > Chemical signal1 > Flashcards

Chemical signal1 Flashcards

1
Q

3 main types of chemical signals?

A
  1. Endocrine
  2. Paracrine
  3. Authocrine
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2
Q

Endocrine

A

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

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3
Q

Paracrine

A

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.

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4
Q

Juxtacrine

A

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

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5
Q

Autocrine

A

The chemical agent acts on the cell that secreted it

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

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6
Q

What do chemical messenger require?

A 
Inducing agent(ligand)
Recepto
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7
Q

Inducing agent(ligand)

A

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

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8
Q

Receptor

A

-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

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9
Q

Intracellular

A

For lipid soluble messengers(steroid hormone)

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10
Q

Extracellular

A

For lipid insoluble

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

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11
Q

Multiple signals maybe integrated(pathway cross-talk)

A

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

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12
Q

Receptor down regulation

A

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

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13
Q

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

A

Agonists activates the receptor ( mimetics)

Antagonists inhibit the receptor

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14
Q

Signal amplification

A

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

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15
Q

Which chemical messenger do not require a second messenger system?

A

Steroid hormone

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16
Q

Steroid hormone

A
  • 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
17
Q

Steroid hormone process

A
  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
18
Q

The general flow of information during cell signaling

A
  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
19
Q

Membrane receptor linked cell signaling pathway

A 
Result in activation of second messenger(Intracellular messenger)
CAMP
IP3
DAG
Ca2+
NO
20
Q

Specific membrane receptor-linked second messenger pathway

A

G-protein linked receptor

21
Q

G-protein linked receptors

A
  • 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)
22
Q

2 classes of G-proteins

A

Large heterotrimeric G-protein

Small monomeric G-protein

23
Q

Large heterotrimeric G-proteins

A

-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

24
Q

Small monomeric-G protein

A

Consist of a single protein (Ras family members)

Similar to G alpha

25
Q

G-protein receptor function

A
  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
26
Q

Some G proteins act to elevate cAMP via?

A

Adenylyl cyclase

27
Q

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

A
  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
28
Q

The second messenger,cAMP has many cell specific effects:

A
  • 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)
29
Q

Another G protein target is..

A

Phospholipids C

30
Q

Phospholipase C

A

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

31
Q

Gq

A

The G protein that activates Phospholipase C

32
Q

Function of Phospholipase C

A
  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
33
Q

Cytosolic ca

A
  • 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)
34
Q

What proteins help to regulate cytosolic ca2+

A
  • 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
35
Q

Ca2+ effector proteins

A

Calcineurin

Calmodulin

36
Q

Calcineurin

A

Ca2+ activated protein phosphotase

37
Q

Calmodulin

A

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

38
Q

EF hand domain

A

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

Cell Physio (5 decks)

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