Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cell Phys > Lec 14: Chemical Signals II > Flashcards

Lec 14: Chemical Signals II Flashcards

1
Q

(Protein Kinase-Associated Membrane Receptors)

Membrane receptors that…

A

directly transmit signals via phosphorylation of intracellular protein targets (protein kinase receptors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

(Protein Kinase-Associated Membrane Receptors)

  • The receptor is a…
  • activated upon…

2 Main Types:

  • Many ____ _____ bind to protein kinase receptors
  • Important roles in…
A
  • …kinase
  • …ligand binding
  1. ) Receptor Tyrosine Kinases (RTKs)
  2. ) Receptor Serine/Threonine Kinases (RSTKs)
  • growth factors
  • cell proliferation, growth, and cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

(Receptor Tyrosine Kinases)

Examples: (4)

A
  1. ) Insulin receptor
  2. ) Insulin-like growth factor-1 (IGF-1) receptor
  3. ) Nerve growth factor receptor
  4. ) Epidermal growth factor (EGF) receptor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

(Receptor Tyrosine Kinases)
Genereal Structure:
- Single…

  • Single…
  • _______ portion – contains…
  • _______ portion: (2)
A
  • Single polypeptide chain (may oligomerize upon ligand binding)
  • Single transmembrane domain
    • Extracellular portion – contains ligand binding domain (N-term)
    • Intracellular portion: (2) (C-term)
      1. ) Tyrosine kinase domain
      2. ) Multiple tyrosine residues that can be autophosphorylated
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

(EGF Receptor)
- EGF binding site on…

  • Single… (2)
  • ______ & ______ on the intracellular portion
A
  • extracellular portion
  • transmembrane domain
    1.) Single pass
    2.) Synthesized at RER
    ERSS & Single Internal Stop-Transfer (C-terminus is in cytoplasm)
  • Tyrosine kinase domain & multiple tyrosine residues (at cytosolic tail) on intracellular portion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

IGF-1 Receptor is similar to…

Two ____-____ _____: (2)

IGF-1 binding site on…

Single transmembrane domain for… (2)

On the intracellular portion…

Encoded by…
- The initial polypeptide is then…

A

Insulin receptor

2 cross-linked dimers:

  1. ) a-subunit
  2. ) b-subunit

…extracellular portion

…each dimer

  1. ) ERSS
  2. ) Single Internal Stop-Transfer (COOH terminus is in cytoplasm

…Tyrosine kinase domain & multiple tyrosine residues

…a single gene & a single mRNA
- …glycosylated and cleaved into the subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

EGF stimulates

A

the growth, repair, and proliferation of epithelial & mesenchymal cells and tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

EGF (ligand) binding results in: (3)

A
  1. ) Receptor aggregation (dimer)
  2. ) The tyrosine kinases of the two receptors phosphorylate the tyrosine residues on the opposing receptor (autophosphorylation) to form phosphotyrosine
  3. ) Following autophosphorylation, the cytosolic portion undergoes a conformational change that results in interactions with additional cytosolic signaling proteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

EGF Receptor Signaling: (

A

1.) The ligand (EGF) binds to the receptor (EGF Receptor) & activates via dimerization & autophosphorylation (previous slide)

  1. ) Following activation, proteins that bind to phosphotyrosine can then interact with the receptor: (These proteins have SH2 domains that bind phosphotyrosine)
    1. ) GRB2 – Growth factor receptor-bound protein 2 - activates Ras (binds GTP) via Sos (a GEF, son of sevenless) (step 3)
    2. ) PLCg – to form DAG and IP3 from PIP2 (step 4)
  2. ) Following Ras activation (GTP binding), Ras initiates a series of phosphorylation steps (relay the message): Raf, MEK, MAPK, Ets, Jun
  3. ) . Ets and Jun (along with fos) then promote the expression of genes related to growth and mitosis

5.) Following signal termination, Ras is inactivated by GAPs (GTPase-activating proteins).
(The GAP facilitates GTP hydrolysis by Ras)
(Thus, Ras is now bound to GDP and is inactive)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Raf =

MEK =

MAPK =

Ets =

Jun =

A

= (mitogen activated protein kinase kinase kinase, MAPKKK)

= (mitogen-activated protein kinase kinase, MAPKK)

= (mitogen-activated protein kinase)

= (E-twenty six, family of transcription factor)

= (early response transcription factor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Mitogen =

In this example, ______ is the mitogen

A

= agent that stimulates mitosis.

EGF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Insulin & IGF-1 receptors:
1.) Different RTKs have…

  1. ) The Insulin stimulates…
    • The Insulin receptor (RTK), upon ligand binding and autophosphorylation, activates…
    • IRS-1 in turn activates…
    • via…
  2. ) IGF-1 stimulates ___ ______ via activation of:
  3. ) Take home message =
A

1.) different substrates!!

  1. ) glucose uptake into cells
    • …IRS-1 (insulin receptor substrate-1) via phosphorylation
    • …downstream proteins that cause an elevation in glucose transporters in cell membrane
    • …regulated secretion
  2. ) ….cell growth
    • IRS-1, which then activates downstream proteins that cause an elevation in muscle protein synthesis.

4.) = Different RTKs activate different cellular signaling pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

(Receptor Serine Threonine Kinases (RSTK))

  1. ) Some growth factors utilize…
  2. ) Example =
  3. ) Regulate…
  4. ) Generally involve 2 types of receptors that function together:
    • Both receptors are…
    • Send…
A
  1. ) RSTKs to initiate intracellular signals
  2. ) TGFb family of receptors
  3. ) a wide variety of cellular functions (Proliferation, apoptosis, cellular development & differentiation)

4.) Type I and type II receptors (cooperatively bind the ligand, TGF or similar molecules like myostatin)
- serine/threonine kinases
- intracellular signals via the phosphorylation of R-Smad (receptor regulated Smad)
R-Smads are a family of transcription factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

R-Smads are

A

a family of transcription factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q
  1. ) Prior to binding the ligand, the receptors (type I and II) are located…
  2. )Upon binding the ligand, the receptors…
  3. ) The phosphorylated type I receptor then binds…
  4. ) The type I receptor then…
  5. ) The phososphorylated R-Smad interacts…
  6. ) The R-Smad has…
A
  1. ) individually at the cell surface
  2. ) cluster and upon association with one another, the type II receptor phosphorylates the type I receptor
  3. ) a complex of proteins (including an anchoring protein and R-Smad)
  4. ) phosphorylates R-Smad (a transcription factor)
  5. ) with Smad-4 proteins and is translocated to the nucleus where it can influence gene expression in association with other transcription factors and co-regulators
  6. ) a nuclear localizing signal, that is exposed upon phosphorylation allowing it to move into the nucleus with Smad4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Myostatin =

Myostatin receptor =

A

= TGFb family member

= activin receptor (RSTK)
Type I and II activin receptors (as above)

17
Q

Myostatin Functions: (4)

  • Acts as a…
A
  1. ) Myostatin binds to the receptor proteins
  2. ) Causes phosphorylation of type I and then recruitment & phosphorylation of R-Smad
  3. ) R-Smad enters nucleus with Smad-4
  4. ) Changes in gene expression –> suppress growth
    - …muscle growth inhibitor, secreted by muscle and impacts muscle in an autocrine and endocrine manner.
18
Q

(Myostatin)
Knock out myostatin =

Occurs naturally: (5)

A

= elevated muscle growth

Bovine - Double muscled cattle
Pigs
Mice
Dogs
Human
19
Q

Epinephrine is associated with

A

the “fight or flight” response

20
Q

Epinephrine (adrenalin), is a hormone that stimulates

A

a variety of cellular effects in different tissues (“fight or flight” response)

21
Q

(Epinephrine)
How can it have such a diverse array of functions?
& 2:

A

Even some that are opposite in different tissues:

  1. ) Smooth muscle relaxation in respiratory system
  2. ) Smooth muscle contraction in some blood vessels
22
Q 
(Epinephrine)
How can it have such a diverse array of functions?  
1.) Different...
2.) Linked to...
3.) Linked to different...
A
  1. ) receptor subtypes in different tissues
  2. ) different G-proteins and
  3. ) intracellular signaling pathways and downstream targets
23
Q 
(Epinephrine)
Adrenergic receptor subtypes:
(all G-protein coupled)
a1 = 
a2 =
b1 =
b2 =
b3 =
A 
a1 = activates PLC via Gq
a2 = activates adenylyl cyclase (Gs)
b1 = activates adenylyl cyclase (Gs)
b2 = activates adenylyl cyclase (Gs)
b3 = activates adenylyl cyclase (Gs)
24
Q

(Smooth muscle responses to adrenergic stimulation)

Respiratory passage ways =

  • Have…
  • Activate…
A

= trachea, bronchi, bronchioles

  • b2-adrenergic receptors
  • Gs –> inc. adenylyl cyclase activity –> inc. cAMP –> smooth muscle relaxation –> airway dilation (bronchodilation)
25
Q

(Smooth muscle responses to adrenergic stimulation)

Vasculature of…

  • Have…
  • Activate…
A

…(arteries & arterioles) skin, GI, kidney, brain

  • a1-adrenergic receptors
  • Gq–> inc. PLC activity –> inc. IP3 –> inc. cytosolic [Ca2+] –> smooth muscle contraction –> vessel constriction –> decreased blood flow
26
Q

(Smooth muscle responses to adrenergic stimulation)

Vasculature…

  • Have…
  • Activate…
A

…(arteries & arterioles) of skeletal & cardiac muscle

  • b2-adrenergic receptors
  • Gs–> inc. adenylyl cyclase activity –> inc. cAMP –> smooth muscle relaxation –> vessel dilation –> increased blood flow
27
Q

Adrenergic agonists (sympathomimetics): (3)

A
  1. ) Phenylephrine (nasal decongestant)
  2. ) Ephedrine (pseudoephedrine)
  3. ) Clenbuterol, salbutamol (albuterol), metaproterenol, ractopamine (asthma treatments)
28
Q

(Adrenergic agonists (sympathomimetics) // 1.) Phenylephrine (nasal decongestant))

  1. ) is a…
  2. ) stimulates…
A
  1. ) a1-adrenergic agonist (stimulates PLC and smooth muscle contraction)
  2. ) vasoconstriction of nasal blood vessels, results in reduced blood flow to the nasal mucosa, relieves swelling of nasal mucosa
29
Q

(Adrenergic agonists (sympathomimetics) // 2.) Ephedrine (pseudoephedrine))

  1. ) is a…
  2. ) functions:
  3. ) actions on…
  4. ) Also used…
A
  1. ) Same as a1-adrenergic agonist, but also induces the release of noradrenaline
  2. ) Stimulant actions (stimulates heart rate) result from direct and indirect activation of α- and β-adrenergic receptors (via noradrenaline release)
  3. ) b-adrenergic receptors allow for airway dilation (bronchodilation)
  4. ) illicitly to manufacture methamphetamines
30
Q

(Adrenergic agonists (sympathomimetics) // 3.) Clenbuterol, salbutamol (albuterol), metaproterenol, ractopamine (asthma treatments))

  1. ) is a…
  2. ) functions…
A
  1. ) b2-adrenergic agonists (stimulate adenylyl cyclase and smooth muscle relaxation), allow for airway dilation (bronchodilation)
  2. ) Also used to increase muscle mass, somehow activate the IGF-1 growth related pathway (at Akt)
31
Q

Adrenergic antagonist example

A

Propranolol

32
Q

(Adrenergic antagonist/Propranolol)

  1. ) function =
  2. ) used for treating…
  3. ) Results in…
A
  1. ) Blocks the b receptors
  2. ) high blood pressure and heart pain (angina) and heart arrhythmia
  3. ) reduced blood pressure by:
    - Reducing heart rate
    - Reducing the force of heart contractions
33
Q

(Insulin)

is a…

Involved in…

Secreted by…

Actions: (3)

A

…Hormone (protein) – (endocrine system)

…the regulation of blood glucose levels

…the b-cells of the pancreas (in the Islets of Langerhans, endocrine portion of the pancreas)

  1. ) Insulin is generally secreted into the blood after a meal
  2. ) Acts to increase delivery of glucose into most cells of the body
  3. ) Thereby decreasing blood glucose
34
Q

Insulin Response: (4)

A
  1. ) Following a carbohydrate-rich meal, glucose gets absorbed at the intestines, and blood glucose increases.
  2. ) This causes insulin to be secreted into the blood.
  3. ) Since insulin increases the number of GLUT4 transporters in the cell membrane of several tissues (including muscle), blood glucose slowly decreases to resting values and insulin levels decrease back to resting values as well.
  4. ) Glucagon is another hormone that has the opposite impact on blood sugar tending to increase blood sugar during periods of “fasting”.
35
Q

How does a rise in blood glucose cause insulin secretion? (7)

A
  1. ) A rise in glucose in blood will cause glucose to enter the b-cell via the GLUT2 transporter (simple diffusion-based).
  2. ) In the b-cell, glucose enters the glycolytic pathway, is metabolized, and ATP is produced.
  3. ) ATP inhibits a specific K+channel (KATP channel, ATP sensitive-K+ channel).
  4. ) Results in depolarization.
  5. ) Depolarization cause voltage-gated Ca2+ channels to open.
  6. ) Ca2+ enters the cell and binds to synaptotagmin.
  7. ) Insulin is secreted.
36
Q

(Diabetes mellitus (DM))
Due to…

Causes…

A

…elevated blood sugar levels over a prolonged period:

…Frequent urination, increased thirst, and increased hunger
Cardiovascular disease, stroke, chronic kidney disease, foot ulcers

37
Q

(Diabetes mellitus (DM))

Type 1 DM results from…

Type 2 DM begins with…

  • Cells (largely muscle cells)…
  • May lead to…
  • Potential risk factors are…
A

…the pancreas’ failure to produce enough insulin due to loss of beta cells. Likely due to autoimmune disorder.

…insulin resistance:

  • fail to respond to insulin properly.
  • inability to produce insulin.
  • excessive body weight and insufficient exercise.
38
Q

(Diabetes mellitus (DM))

Gestational diabetes…

A

Some pregnant women, without a previous history of diabetes, develop high blood sugar levels.

Cell Phys (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions