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MCM II > Lec 3 receptors and cell signaling > Flashcards

Lec 3 receptors and cell signaling Flashcards

1
Q

What is endocrine signaling?

A

signal is transported via blood (hormone) long distance freely diffusing signal (shorter side minutes)

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2
Q

example of endocrine signaling?

A

epinephrine

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3
Q

what is paracrine signaling?

A

signal diffuses to neighboring target cell of a different type Local signalling. short time

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4
Q

example of paracrine signaling?

A

testosterone

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5
Q

What is autocrine signaling?

A

secreting cells express surface receptors for the signal

same cell or same cell type

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6
Q

example of Autocrine signaling?

A

interleukin-1

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7
Q

what is direct/juxtacrine signaling?

A

signal binds to signaling cell which then binds to receptor on the target cell

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8
Q

What is an example of a direct/juxtacrine signaling?

A

heparin binding epidermal growth factor

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9
Q

What are the two types of signaling molecules?

A

water soluble (hydrophilic) and lipid soluble (hydrophobic)(lipophilic)

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10
Q

What is the mechanism of hydrophilic signaling?

A

Cannot penetrate the membrane.

so reacts with receptors on the cell surface

This leads to production of the second messengers

Triggers a downstream response.

(shorter half life seconds to minutes)

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11
Q

What receptors are involved in downstream signaling?

A
  1. G-protein coupled receptors (GPCR)
  2. Receptor tyrosine kinase (RTK)
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12
Q

examples of hydrophilic signal molecules

A

epinephrine, insulin, glucagon

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13
Q

What is the mechanism of lipophilic signaling?

A

pass through the cell membrane of target cell

ligand attaches to specific site in the cell

signaling molecule-receptor complex acts as a transcription factor (regulates transcription of specific genes)

long-acting hours to days

(steroids)

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14
Q

Where are the locations of lipophilic signaling receptors?

A

Cytoplasmic receptors

nuclear receptors

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15
Q

how do cytoplasmic receptors work?

A

in an inactive from of HSP 90

upon binding of ligand HSP dissociates

hormone receptor complex then goes to nucleus

binds DNA sequence hormone response element (HRE)

(promoter region of genes)

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16
Q

How do nuclear receptors work?

A

already in nucleus bound to DNA

protein bind allows addition of additional proteins and activates

17
Q

Types of receptors?

A
18
Q

What is the structure of a G-coupled protein receptor? (GCPR)

A
19
Q

Steps of G protein signal relay

A
  1. ligand binds to receptor
  2. conformational change occurs in receptor
  3. GPCR able to interact with and bind G protein
  4. RECEPTOR THEN ACTS AS A GEF (GUANIDINE EXCHANGE FACTOR)
  5. conformation of Galpha protein is changed such that it kics out GDP and GTP binds
  6. Galpha actived and binds and activates or inhibits effector mol
  7. effector mol catalyzes reactions that produce secondary molecules
20
Q

What is GAP and what does it do?

A

GTPase activating protein

accelerates the hydrolyzing of bound GTP to GDP and phosphate.

21
Q

Gs GPCR signal

A

Stimulates adenylate cyclase (makes cAMP)

cAMP activates protein kinase A

Phosphylation via PkA

22
Q

Gi GPCR signaling

A

Inhibits adenylate cyclase

no cAMP produced

so PKA not activated so no phosphorylation

23
Q

Gt GPCR signaling

A

(uses light (photons)) (T for Tan)

stimulations cGMP phosphodiesterase

breaks down cGCP to 5’-GMP

turns off something that was already on

24
Q

Gq GPCR signaling

A

activates phospholipase C

activates PIP2

makes DAG

which activates PKC

phosphorylation of target proteins

(IP3 releases Ca2+ which helps activate PKC and also

activates CA calmodulin complex)

25
Q

what binds to activate Gs protein

A

epinephrine (Beta-adrenergic receptor) and histamine

26
Q

examples of what binds to activate Gi protein

A

epinephrine/norepinephrine (alpha-adrenergic receptor)

Dopamine

27
Q

examples of what binds to activate Gq protein

A

acetylcholine

28
Q

Examples of what binds to activate Gt protein?

A

Light (photons)

29
Q

Epinephrine and G proteins

A

non-selective agonist of all adrenergic receptors (alpha 1, alpha 2, beta 1, beta 2, beta 3

multiple GPCR signaling pathways

30
Q

Can G protein-coupled receptors have multiple responses?

A
31
Q

what hydrolyzes cAMP and cGMP

A

cAMP/ cGMP phosphodiesterase

32
Q

what can inhibition of cGMP phosphodiesterase cause?

A

can cause increase in cGMP due to no hydrolyze

leads to smooth muscle relaxation and vasodilation

(Viagra, levitra, cialas)

33
Q

NO causes what?

A

diffuses in muscle and activated guanylate cyclase

smooth muscle relaxation and vasodilation

nitrates lower blood pressure

Dont take with cGMP PDE inhibitor or too low BP

34
Q

Mechanism of Cholera

A

Gs

contaminated water

covalent modification of alpha subunits ADP ribosylation of Arg decreases GTPase activity

Gs(alpha) remains active stims adenylate cyclase

too much cAMP

cells open Cl- channels

Na+ soon follows loss of water/electrolytes

35
Q

Mechanism of Pertussis

A

Gi

ADP ribosylation of Cys on Gi(alpha) prevents alpha unit dissociation in G protein complex

less inhibition of AC and overproduct cAMP

loss of fluids and excessive mucous in airway epithelial cells

(Cl- ion out Na+ follows then water)

36
Q

Signal desensitization

A
37
Q

What does a G protein receptor kinase do?

A

(GRKs)

phosphorylate GPCRs (ATP used)

arrestin binds 3rd intracellular loop

prevents Galpha interact with loop

Galpha-GDP does not get converted to Galpha-GTP

inactive G protein complex

MCM II (11 decks)

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